Method of treating or ameliorating skin conditions with a magnetic dipole stabilized solution

ABSTRACT

The present invention is directed to methods for treating or ameliorating skin conditions, diabetic conditions, cardiovascular conditions, cancer, infections or metal poisoning, enhancing performance, or providing nutritional support, comprising administering to a subject in need thereof compositions comprising a magnetic dipole stabilized solution (MDSS). The MDSS solution may include additional components and can be provided in a kit.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/398,233, which was filed Jan. 4, 2017 and is a continuation of U.S.patent application Ser. No. 14/017,811, which was filed Sep. 4, 2013 andwas a continuation of U.S. patent application Ser. No. 13/811,547, whichis now abandoned and was a 371 of PCT/US2011/044947, which was filedJul. 22, 2011 and claimed the benefit of U.S. Provisional PatentApplication No. 61/366,853, filed Jul. 22, 2010, U.S. Provisional PatentApplication No. 61/366,852, filed Jul. 22, 2010, U.S. Provisional PatentApplication No. 61/366,845, filed Jul. 22, 2010, and U.S. ProvisionalPatent Application No. 61/366,844, filed Jul. 22, 2010, all of which areincorporated herein by reference as if fully set forth herein.

FIELD OF THE INVENTION

The present invention is directed to methods involving theadministration of a composition comprising a magnetic dipole stabilizedsolution to a subject in need thereof for treating or ameliorating skinconditions, diabetic conditions, cardiovascular conditions, cancer andinfections, chelating, reducing the amount of metal in a subject orincreasing the amount of excretion of metal from a subject, providingnutritional support or enhancing performance.

BACKGROUND

A magnetic dipole stabilized solution which can be an electro-activatedwater is sterile and non-pyrogenic and is produced by exposing the waterto a strong electrical (magnetic) field force in a tightly isolated andfully enclosed reactor space. It is capable of producing both a negative(cathodic) and a positive (anodic) stream of activated water.

Electrolysis of water, including saline solutions, is known forantimicrobial properties and for use on hard surfaces (U.S. Pat. Nos.4,236,992 and 4,316,787). Electrolyzed water has been administered fortherapeutic use through ingestion or topical administration. PublishedU.S. Patent Application No. 20060008908 discloses a beverage containingelectrolyzed water and a cesium or rubidium salt for promotinglongevity. The application notes that there may be anelectro-physiological imbalance that is the origin of disease and thatelectrolyzed water can restore optimal pH. The electrolyzed water isdisclosed as an alkaline water. Published U.S. Patent Application No.20050074421 discloses an acidic electrolyzed water composition. It isfor external use and is purported to be a cosmetic and a hair growingtonic. An electrolyzed water composition is disclosed in U.S. Pat. No.6,544,502. An antibiotic can be admixed in the water and used topicallyto treat acne. An electrolyzed saline solution containing regulatedamounts of ozone and active chlorine species is described in U.S. Pat.No. 5,622,848. The solution can be given intravenously.

Cardiovascular diseases, which include coronary heart disease (heartattacks), cerebrovascular disease, raised blood pressure (hypertension),peripheral artery disease, rheumatic heart disease, congenital heartdisease and heart failure, derive from dysfunctional conditions of theheart, arteries, and veins that supply oxygen to vital life-sustainingorgans, including the brain and the heart itself. Major causes ofcardiovascular disease are tobacco use, physical inactivity and anunhealthy diet.

Heart attacks and strokes are mainly caused by a blockage in the innerwalls of the blood vessels that prevents blood from flowing to the heartor the brain. Arteriosclerosis and atherosclerosis are excess buildup offat or plaque deposits, respectively, that cause narrowing of the veinsthat supply oxygenated blood to the heart and may lead to ischemic heartdisease, an obstruction of blood flow to the heart. Excess fat or plaquebuildup may also cause high blood pressure (hypertension), a diseaseknown as “The Silent Killer” because the first warning sign is an anginaattack, a deadly heart attack or a stroke. Kidney disorders, obesity,diabetes, smoking, excess alcohol, stress, and thyroid and adrenal glandproblems can also exacerbate a high blood pressure condition.

Damage to the heart tissues from cardiovascular diseases or heartsurgery disrupts the natural electrical impulses of the heart andresults in cardiac arrhythmia. Sudden fluctuations in heart rate cancause cardiac irregularities and insufficiencies, includingpalpitations, supraventricular tachycardia, fibrillation faintness ordizziness, and even initiate a heart attack. Mismatch of cardiac outputduring strenuous exercise may lead to muscle damage, induce fatigue andaffect athletic performance. Arteries spasm and irregular contractionand expansion of blood vessels in the brain may reduce flow of bloodfrom the occipital lobe and trigger migraines. Levels of total bloodcholesterol above 250 mg/dL, LDL cholesterol above 130 mg/dL (3.0mmol/L), HDL cholesterol below 35 mg/dL and lipoprotein(a) level greaterthan 30 mg/dL may also lead to a heart attack or stroke.

Infections of the heart, known as carditis and endocarditis, may occuras a result of a weak immune system, liver problems, heart surgery, orfrom an autoimmune disorder like rheumatic fever.

Heavy smoking may cause Buerger's disease, also known asthrombophlebitis obliterans, an acute inflammation and thrombosis(clotting) of arteries and veins of the hands and feet, which is oftenassociated with intense pain in the extremities, claudication in thefeet and/or hands, numbness and/or tingling in the limbs, skinulcerations, gangrene and Raynaud's phenomenon, a condition in which thedistal extremities turn white upon exposure to cold.

Peripheral arterial occlusive disease may cause diabetic ulcers, whichare the most common foot injuries leading to lower extremity amputationin diabetic patients.

Research indicates the course of events which leads to the loss offunction, deterioration, destruction and death of the human cell and toa large extent research relates to the issue of human cellular relianceon oxygen metabolism, which occurs intracellularly. Oxygen uptakeintracellularly is governed by the metabolic need for energy and takesplace within the mitochondria to produce ATP, the cell's energy source.Such chemical reactions are not 100% efficient and the resultant releaseof highly reactive oxygen species cytoplasm is responsible for cellulardamage. The relative amount of such oxygen by-products is less than theamount produced in many other mammal species, however, such by-productsare highly toxic. Such examples include superoxide and hydroxylradicals, which can cause oxidative damage to cells and tissues.Superoxide and water produce concentrated hydrogen peroxide and iscapable of intense skin damage within a few seconds, when applied tohuman skin. The same reaction occurs intracellularly within thecytoplasm and causes severe damage. The cells are protected by means ofenzymes to destroy peroxide radicals continually, however, such defensesare not 100% efficient with the result that chemical destruction ofcells occurs.

Free oxygen radicals, also known as reactive oxygen species (ROS), causemuch damage to macromolecules, including lipids, proteins and nucleicacids. One major toxic effect of oxygen radicals is damage to cellularmembranes, including the plasma, mitochondrial and endo-membranesystems, which is initiated by lipid peroxidation and is accompanied byincreased membrane rigidity, decreased activity of membrane-boundenzymes, altered activity of membrane receptors and altered membranepermeability. Furthermore, oxygen radicals can also directly attackmembrane proteins and induce lipid-lipid, lipid-protein andprotein-protein crosslinking, which in turn affects membrane function.

Because of their reactivity, free oxygen radicals may react with DNA,resulting in mutations that can adversely affect the cell cycle andpotentially lead to cancer and malignancies. Moreover, oxygen freeradicals are involved in cardiovascular diseases, the aging process,neurodegenerative diseases, including ALS, Parkinson's disease andAlzheimer's disease, cataractogenesis, atherosclerosis, diabetesmellitus, ischemia-reperfusion injury, kwashiorkor, senile- anddrug-induced deafness, schizophrenia, atherosclerosis andalcohol-induced liver damage.

There is strong evidence in the literature that free oxygen radicalsoxidize low density lipoprotein (LDL), which is then engulfed byphagocytes to form foam cells and plaques in the cardiovascular wall.These plaques harden and narrow the blood vessels and impair blood flow,thus depriving the heart of oxygen and nutrients. In addition, ischemiais often followed by reperfusion injury, which is caused by inadequatesupplies of intracellular antioxidants. Ischemia and reperfusion are amajor cause of strokes. There is also increasing evidence that mismatchof cardiac output during strenuous exercise causes release of freeoxygen radicals, which contribute to muscle damage and induce fatigueand/or injury. Moreover, it has been reported that the activity of theanti-oxidant enzymes superoxide dismutase (SOD), catalase (CAT) andglutathione peroxidase (GSH-Px) is significantly lower in subjectssuffering from migraine. SOD is known to protect againstvasoconstriction or vasospasm induced by superoxide radicals. Migraineis a potential risk factor or marker for atherosclerosis-relateddiseases.

An example of cell damage caused by oxygen reactions is damage to theDNA. It is evident that DNA destructive reactions occur daily in normalman. Most of these are repaired enzymatically, if not, such cellsreproduce out of control, with resulting neoplasms. However, thelong-term aging effects of endogenous damage, is exemplified bywrinkling and hardening of the skin and arteries with age. Skin andarteries consist of collagen and elastin tissue. Collagen is the majorprotein of white fibers of the body's connective tissues, cartilage andbone. Elastin is the major connective tissue of structures such as largeblood vessels and skin. It is elastin that enables these structures tostretch and resume to original size and shape. Free radical changesdescribed above yields a pathology, which leads to neoplastic changes,atherosclerosis and loss of elasticity of the skin. The pathology iscentered on the cell membranes in all organs and affected by the supplyof nutrients, vitamins, and nucleic acids through the microcirculation.Recent scientific studies have shown that this mechanism progresses fromfree radical reactions to oxidative products, which damages cells andtissues. This simultaneously affects all cells, tissues and organsthroughout the body and is progressively insidious. These processesinvolve a fundamental aspect of homeostasis and cell physiology.

The clinical significance of the chemical damage generated in livingcells, has been documented. It is therefore necessary to develop methodsto inhibit damage caused by these mechanisms.

Circulation disorders are common disorders amongst the populace. It maybe a severe medical challenge and may lead to limb loss and a markedreduction in quality of life. Circulation disorders are often diagnosedat a late stage of the disease. Non-healing small wounds are the earlycharacteristics of poor circulation. Such wounds are often treatedwithout the underlying cause being correctly diagnosed. This results inulceration, discomfort and pain and may lead to limb amputation. Poorcirculation can also manifest itself in a patient being able to onlywalk short distances, and be the cause of severe cramps. Other examplesare patients with no feeling in their toes and or feet and severediscoloration of either the hand or foot.

A general condition has been identified in this disease as being part ofan autoimmune syndrome manifesting as a general inflammatory conditionof the vascular system, more specifically vasculitis. Vasculitis may beconsidered an inflammatory syndrome with structural alterations of thevascular wall, complicated by lumen occlusion, leading to tissueischemia. Vessels of any size may be altered in systemic vasculitis butin cutaneous forms alteration affects small vessels, especially thosepost-capillary. The various forms differ by age of onset, affectedorgan, and presence of periods of remission and exacerbation, amongstother features. Sometimes they may also be superimposed to otherwell-defined diseases, as vascular disorders, identified as secondaryconditions such as neoplasia, allergic reactions, and infections.

Infections can promote inflammation of the vascular intima wall of anydiameter and in any organ. Palpable purpura is the most commonmanifestation of vasculitis, although erythematous macules, nodule,ecchimoses, erosions, ulcerations, hemorrhagic blisters, necrosis, andgangrene may also occur. Skin can be the target organ in this type ofvascular pathology. The relative frequency of vasculitis of the skin maybe the first manifestation of a very severe systemic disease.

Relative and or absolute ischemia caused by vascular disease such assclerosis resulting from aging, results in compromised poor blood flowto tissues and cells. This results in a lack of nutrients and oxygen atcellular level from reaching the cells, with the resulting symptoms ofageing. This is manifested by such symptoms as a loss of mental agility,alertness, memory loss and other conditions commonly seen in senescence.In normal metabolism most of the metabolic energy is used to maintaingradients across the cell membrane. The provision of nutrient substratesis recognized as the best basis for maintaining a level of metabolicactivity and ongoing energy needs in the cell. In these instancesdiseases as manifested by neurodegeneration of aging may also bemodulated. Because neuron function can be disrupted by many substancesin the blood, it is necessary to target the central nervous system bymeans of carrier fluids capable of breaching the blood brain barrier byintroducing charged and or lipid substances into the blood mayaccomplish this. It is known that chemical communication in the brainmay be influenced by norepinephrine, acetylcholine, serotonin, endorphinand many other naturally occurring chemicals in the brain.

The effects of aging may be attributed, on a molecular level, to theoxidative processes in the cell which is harmful to proteins, lipids andnucleic acids. By providing sufficient anti-oxidants, it may be possibleto modulate or even reverse the effects of aging at molecular level.Biological aging processes are part of the increase in disorder atcellular level with the acknowledged difference being that in the caseof a pathological multi-system, atrophy or senescence at cellular level,multi-organ failure may occur. This process is demonstrated by reductionin cellular mass of the organs and may be seen in the aged on autopsy.For instance, the human brain can decrease from an average weight of1500 grams to less than 1000 grams in advanced age.

The senescent organ loses many functions, leading to premature aging,for instance the brain loses its memory retention capability, cannotreact quickly to external stimuli and is unable to memorize newinformation. Loss of mass is also demonstrated in organs such as theliver, kidneys, lymph nodes, skeletal muscle and bones. Correspondingchanges are seen in depleted fat deposits, skin elasticity, brittlebones, low resistance to infection, lack of exercise tolerance andreproductive ability. At the cellular level, aging means inadequate DNArepair, leading to disorder in cell replication Loss of mitosis in thenucleus of the cell, followed by a closing of the microcirculation. Thisresults in so-called cell drop-out and loss of organs, as well asmembrane function, in particular the TNP or transmembrane potential.This process is progressive and affects all organs and tissuesthroughout the body. The etiology and pathogenesis of this conditioninvolves a universal and fundamental aspect of cell physiology.

In any study on aging, two distinct types of cells must be considered.These include normally dividing cells and post-mitotic cells, normallydividing cells are those of the skin, hair and gastrointestinal tract.Thousands of such cells die daily, but are continually replaced withexact replicas until the time of aging begins. This begins in themid-twenties in humans. The second cell type is that which makes up thecentral nervous system, brain and heart. In general, post-mitotic cellsdo not divide or reproduce. Humans are born with a fixed number ofpost-mitotic cells, which lose function and die daily throughout thehuman life span. Death, as a result of aging, occurs when a criticalnumber of post-mitotic cells lose function within a critical organ, suchas the brain.

Congenital defects and infectious disease can strike anywhere. One ofthe most common diseases occurs in the arteries: atherosclerosis.Blockages can occur in veins as well as in arteries, but these tend tobe caused by blood clots, or thrombi, rather than by atherosclerosis.Thrombophlebitis (or often called phlebitis) most commonly involvesclotting of blood and inflammation of a vein in the leg. This can beserious if a portion of the clot becomes detached, travels through theheart and gets pumped to the lung where it blocks a pulmonary artery asa pulmonary embolism. About 10% of people with pulmonary embolism diewithin an hour. Clotting of blood in the veins can occur when blood flowis slow or stagnant. This can occur during long periods ofimmobilization such as when a person is confined to a hospital bed,cramped in a crowded airplane on a long flight or driving for anextended period.

Atherosclerosis (hardening of the arteries) occurs “naturally” withaging as a result of cross-linking of macromolecules like proteins andpolysaccharides. Atherosclerosis refers to the formation and hardeningof fatty plaques (atheromas) of the inner surface of the arteries. Inatherosclerosis, the arteries not only harden, they narrow, sometimesnarrowing so much that hardly any blood can get through. Such narrowsvessels are easily blocked by constriction or objects in thebloodstream.

The internal surface of an artery is covered with a single layer ofendothelial cells that are pressed against each other like flagstones ona terrace. Atherosclerosis begins with injury to endothelial cells,exposing portions of the artery surface below the endothelium. Freeradicals, chemicals in cigarette smoke or other irritants could beresponsible for the injury, as could turbulence and mechanical force dueto high blood pressure. Platelets (round cells half as large as redblood cells) clump around the injured endothelial cells and releaseprostaglandins, which cause the endothelial cells to proliferate likecancer. LDL-cholesterol particles release their fat into the areas madeporous by prostaglandins. Macrophages (scavenger white blood cells)engorge themselves on oxidized LDL-cholesterol until they becomeunrecognizable “foam cells” that invade atheromas. Then the atheromasare hardened by fibrin (which forms scar tissue) and finally by calciumpatches. A vicious circle often arises with scar tissue attracting moreplatelets and LDL-engorged macrophages. Atherosclerosis can occur in anyartery. Most commonly it occurs in the aorta, the artery that receivesblood directly from the heart. Since the aorta is the largest artery inthe body, it is rarely critically narrowed by atheromas. Nonetheless,atherosclerosis can contribute to aneurysms (ballooning of an artery,responsible for only one-fortieth of the mortality rate of heartattack—an aortic aneurysm killed Albert Einstein, who refused to beoperated upon.) The most frequent life-threatening problems, however,are caused by the arteries supplying the heart, the brain and thekidneys, in that order.

Since the blood is 80% water, fats will not dissolve in the blood.Therefore, fats need to be attached to carrier molecules to travelthrough the bloodstream. The principle carrier molecules for fat arealbumin, chylomicrons, Very Low Density Lipoprotein (VLDL), Low DensityLipoprotein (LDL) and High Density Lipoprotein (HDL). Free Fatty Acids(FFAs) are attached to albumin, whereas triglycerides are mainlytransported by chylomicrons and VLDL. Cholesterol and phospholipid areprimarily transported by LDL and HDL. Cholesterol is supplied to cellsprimarily by the attachment of LDL to specific LDL receptors on cellmembranes. Thyroid hormone lowers blood cholesterol by increasing thenumber of LDL receptors on cells. For most people, atherosclerosis dueto excessive LDL-cholesterol in the blood is the result of a high levelof dietary saturated fat resulting in high LDL-cholesterol production bythe liver. The primary function of HDL seems to be to remove excesscholesterol from the bloodstream. LDL can directly release cholesterolinto arterial areas made porous by prostaglandins—whereas HDL can scoopup this loose cholesterol and return it to the liver. Thus, HDLdeficiency can be as serious an atherosclerosis risk as LDL-cholesterolexcess. A 1% reduction in blood cholesterol is generally associated witha 2% reduction in risk of coronary artery disease, within “normal”levels of blood cholesterol.

Free fatty acids are a major source of energy for many organs, includingthe heart. Triglycerides are hydrolyzed into FFAs and glycerol by theenzyme lipase, which is found both inside cells and on the surface ofthe endothelial cells of capillaries. Phospholipid is an essentialconstituent of cell membranes. Cholesterol is also an essentialconstituent of cell membranes, particularly in the nervous system.Cholesterol is also the principle precursor of cortisone and sexhormones. 93% of cholesterol is found in cells and only 7% in plasma.

The coronary calcium scan is a test that assists in showing whether apatient is at risk of developing a coronary artery disease (CAD), bydetermining the presence of plaque (fatty deposits) in blood vessels.The presence and amount of calcium detected in a coronary arteryindicates the presence and amount of atherosclerotic plaque. Sincecalcium deposits appear years before the development of heart diseasesymptoms such as chest pain and shortness of breath, a coronary calciumscan is most useful for people who are at moderate risk of having aheart attack within the next 10 years, and may help doctors decidewhether a patient needs treatment. The calcified plaque burden caused bycalcium deposits is measured with the Calcium Score, also called theAgatston Calcium Score, which is computed for each of the coronaryarteries based upon the volume and density of the calcium deposits. Thecalcified plaque burden does not correspond directly to the percentageof narrowing in the artery but does correlate with the severity of theunderlying coronary atherosclerosis. The score is then used to determinethe calcium percentile, which compares the calcified plaque burden in asubject to the calcified plaque burden in other asymptomatic men andwomen of the same age. The calcium score, in combination with thepercentile, enables the physician to determine the risk of developingsymptomatic coronary artery disease and to measure the progression ofdisease and the effectiveness of treatment.

A score of zero indicates the absence of calcified plaque burden andsignificant coronary artery narrowing, although it does not entirelyrule out the presence of soft, non-calcified plaque or the possibilityof a cardiac event. A subject with a score of zero has a very lowlikelihood of a cardiac event over at least the next 3 years. A scoregreater than zero indicates at least some coronary artery disease. Asthe score increases, so does the likelihood of a significant coronarynarrowing and coronary event over the next 3 years, compared to peoplewith lower scores. Similarly, the likelihood of a coronary eventincreases with increasing calcium percentiles.

Often, there are no symptoms of underlying cardiovascular diseases and aheart attack or stroke may be the first warning. Early medical detectionand treatment is available, however, is not always effective.Angiograms, bypass surgery and angioplasty are invasive and traumaticprocedures associated with high cost and often requiring additionaltherapy and/or intervention.

The use of chelating agents of various types to entrap metal ions usefulin magnetic resonance imaging is well known. Generally, the chelatingagents contain a substantial number of unshared electron pairs ornegatively charged or potentially negatively charged species. Perhapsthe simplest among these is ethylenediaminetetraacetic acid (EDTA)commonly used as a water softener. However, many such agents are known,including, most notably, and commonly used, diethylene triaminepentaacetic acid (DTPA) and tetraazacyclododecanetetraacetic acid (DOTA)and their derivatives. U.S. Pat. Nos. 5,573,752 and 6,056,939, disclosederivatives of DOTA which are coupled to a benzyl or phenyl moietywherein the phenyl ring is substituted by isothiocyanate. Thisisothiocyanate provides a reactive group for coupling to variousadditional compounds. As described in these patents, the isothiocyanategroup can be used to couple the chelate to a targeting agent such as anantibody or fragment thereof.

However, many conditions and diseases are brought on by damage at thecellular and intracellular level. Often the mechanisms for cellularrepair are inadequate or so compromised the cells cannot recover or themechanisms that cause the damage simply overwhelm the cell. The clinicalsignificance of the damage generated in living cells is manifested in adiseased cell or symptoms of an underlying condition. It would bebeneficial to develop methods to facilitate the inhibition of cellulardamage or boost recovery. The presently disclosed subject matteraddresses, in whole or in part, these and other needs in the art.

SUMMARY

It is therefore an object of the invention to provide solutions to theaforementioned needs.

To this end, the invention provides methods of treating or amelioratingskin conditions, diabetic conditions, cardiovascular conditions, canceror infections by administering a magnetic dipole stabilized solution(MDSS) are provided. Also provided are methods of chelating, reducingthe amount of metal in a subject, increasing the amount of excretion ofmetal from a subject, enhancing performance and nutritionalsupplementation by administering a magnetic dipole stabilized solution(MDSS). Thus, in one embodiment, the present invention provides a methodof treating or ameliorating a skin condition, a condition associatedwith diabetes, a condition associated with a cardiovascular dysfunction,a cancer, an infection or metal poisoning in a subject in need thereofcomprising administering to the subject by injection a therapeuticallyeffective amount of a composition comprising a magnetic dipolestabilized solution. Preferably, the magnetic dipole stabilized solutionis an electroactivated water having a negative electrical potential ofabout −990 to about −0.0001 mV, and comprising stabilized oxidativespecies selected from the group consisting of H₂O, O₂, H₂O₂, Cl₂O andH₃O. In one aspect of the invention, the skin condition is skin aging,wrinkles, acne, photodamage, rosacea, scars, eczema, alopecia,hypertrophic scars, keliods, stretch marks or Striae distensae,psoriasis, pruritus, ehlers-danlos syndrome, scleroderma, postinflammatory hyperpigmentation, melasma, alopecia, poikiloderma ofcivatte, viteligo, skin cancers, skin dyschromas, burns or blotchypigmentation. In a preferred aspect of the invention, the skin conditionis acne. In another preferred aspect of the invention, the skincondition is alopecia.

In a different aspect of the invention, the condition associated withdiabetes is obesity, hypertension, hyperlipidemia, fatty liver disease,nephropathy, neuropathy, renal failure, retinopathy, diabetic ulcer,cataracts, insulin resistance syndrome, cachexia, a diabetic foot ulceror a diabetic leg ulcer.

In yet another aspect of the invention, the condition associated with acardiovascular dysfunction is coronary heart disease, cerebrovasculardisease, hypertension, peripheral artery disease, occlusive arterialdisease, angina, rheumatic heart disease, congenital heart disease,heart failure, cardiac insufficiency, palpitations, supraventriculartachycardia, fibrillation, faintness, dizziness, fatigue, migraine, highlevels of total blood cholesterol and/or LDL cholesterol, low level ofHDL cholesterol, high level of lipoprotein, infections of the heart suchas carditis and endocarditis, diabetic ulcer, thrombophlebitis, Raynaudsdisease, claudication, gangrene, atherosclerosis or peripheral arterydisease.

In one embodiment the metal poisoning is chronic. In a differentembodiment, the metal poisoning is acute. Preferably, the metal is aheavy metal selected from the group consisting of calcium, aluminum,beryllium, cadmium, copper, iron, lead, uranium, plutonium, arsenic,molybdenum and mercury.

The composition to be administered in the methods of the invention mayfurther comprise vitamins, salts, acids, vitamers, amino acids, ormixtures thereof, di-methyl amino ethanol and an antibiotic. In apreferred aspect of the invention, the antibiotic is erythromycin orgentamicin. In another preferred aspect of the invention, thecomposition to be administered further comprises lipoic acid and saltsor mixtures thereof in an amount of about 250 mg. In yet anotherpreferred aspect of the invention, the composition to be administeredfurther comprises folic acid in an amount of about 400 mg. Thecomposition may be administered by infusion over a period of about 1minute to about 1 hour. The infusion may be repeated as necessary over aperiod of time selected from about 1 week to about 1 year. In anotherpreferred aspect of the invention, the composition to be administeredfurther comprises an anesthetic selected from the group consisting oflignocaine, bupivacaine, dibucaine, procaine, chloroprocaine,prilocalne, mepivacaine, etidocaine, tetracaine, lidocaine andxylocalne, and salts, derivatives and mixtures thereof. In yet anotherpreferred aspect of the invention, the composition to be administeredfurther comprises heparin.

In a preferred embodiment, the composition to be administered comprisessodium ascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate, cyanobalamin, and electroactivated water.

In yet another embodiment, the invention provides a method of reducingthe amount of metal in a subject in need thereof comprisingadministering to the subject by injection a composition comprising amagnetic dipole stabilized solution. In a preferred aspect, the metal isa heavy metal having an oxidation state of +1, +2 or +3 selected fromthe group consisting of calcium, aluminum, beryllium, cadmium, copperiron, lead, uranium, plutonium, arsenic, molybdenum and mercury.Preferably, the metal is a transition or post-transition state metal.Even more preferably, the metal is a divalent cation. In anotherpreferred aspect of the invention, the magnetic dipole stabilizedsolution is an electroactivated water having a negative electricalpotential of about −990 to about −0.0001 mV, and comprising stabilizedoxidative species selected from the group consisting of H₂O, O₂, H₂O₂,Cl₂O and H₃O. Preferably, the solution comprises lipoic acid and saltsor mixtures thereof in an amount of about 250 mg. In a preferred aspectof the invention, the composition is administered by infusion over aperiod of about 1 minute to about 1 hour. The infusion is repeated asnecessary over a period of time selected from about 1 week to about 1year. In a preferred aspect of the invention, the composition to beadministered in the methods of the invention further comprises ananesthetic and one or more amino acids or salt thereof.

In another embodiment, the invention provides a method of increasing theexcretion of metal or one or more toxins from a subject in need thereof,comprising administering to the subject by injection an effective amountof a magnetic dipole stabilized solution. Preferably, the magneticdipole stabilized solution is an electroactivated water having anegative electrical potential of about −990 to about −0.0001 mV, andcomprising stabilized oxidative species selected from the groupconsisting of H₂O, O₂, H₂O₂, Cl₂O and H₃O.

In yet another embodiment, the invention provides a method of enhancingathletic, cognitive or alertness performance in a subject in needthereof comprising administering to the subject by injection aneffective amount of magnetic dipole stabilized solution. Preferably, themagnetic dipole stabilized solution is an electroactivated water havinga negative electrical potential of about −990 to about −0.0001 mV, andcomprising stabilized oxidative species selected from the groupconsisting of H₂O, O₂, H₂O₂, Cl₂O and H₃O. The composition may beadministered by infusion over a period of about 1 minute to about 1hour. The infusion may be repeated as necessary over a period of timeselected from about 1 week to about 1 year within about 24 hours, withinabout one week or within about one month of the performance. In apreferred aspect of the invention, the magnetic dipole stabilizedsolution comprises sodium ascorbate, magnesium chloride 2H₂O, 2di-methyl amino ethanol HCl, thiamine, riboflavine, nicotinamide,pyridoxine, calcium pantothenate, cyanobalamin and electroactivatedwater. In another preferred aspect of the invention, the magnetic dipolestabilized solution comprises from about 100 mg to about 500 mg sodiumascorbate; from about 100 mg to about 500 mg magnesium chloride 2H₂O;from about 100 mg to about 500 mg 2 di-methyl amino ethanol HCl; fromabout 1 mg to about 100 mg thiamine; from about 1 mg to about 100 mgriboflavine; from about 1 mg to about 300 mg nicotinamide; from about 1mg to about 100 mg pyridoxine; from about 1 mg to about 100 mg calciumpantothenate; from about 100 μg to about 500 μg cyanobalamin; andelectroactivated water.

In a further embodiment, the invention provides a method of providingnutritional support to a subject in need thereof comprisingadministering to the subject by injection an effective amount ofmagnetic dipole stabilized solution. Preferably, the magnetic dipolestabilized solution is an electroactivated water having a negativeelectrical potential of about −990 to about −0.0001 my, and comprisingstabilized oxidative species selected from the group consisting of H₂O,O₂2, H₂O₂, Cl₂O and H₃O. The subject may be a healthy individual, or maybe suffering from a malady selected from the group consisting ofmalnutrition, cachexia, diabetes, severe food allergies, short gutsyndrome, cystic fibrosis, pancreatic disease, gastroenteritis,inflammatory bowel disease, intractable diarrhea, protein maldigestion,necrotizing enterocolitis, infectious diseases, hypermetabolism, trauma,eosinophilic gastroenteritis and gastroesophogeal reflux. In a preferredaspect of the invention, the magnetic dipole stabilized solutioncomprises one or more trace metals selected from the group consisting ofZn, Se, Cu, Mn and Fe. In a preferred embodiment, the subject receivingnutritional support has special dietary needs. Preferably, the dietaryneeds are associated with athletes, children, obese subjects, subjectsundergoing chemotherapy for cancer, AIDS patients, malnourished subjectsor subjects in a comatose state. In a preferred aspect of the invention,the magnetic dipole stabilized solution is an electroactivated watercomprising from about 100 mg to about 500 mg sodium ascorbate; fromabout 100 mg to about 500 mg magnesium chloride 2H₂O; from about 100 mgto about 500 mg 2 di-methyl amino ethanol HCl; from about 1 mg to about100 mg thiamine; from about 1 mg to about 100 mg riboflavine; from about1 mg to about 300 mg nicotinamide; from about 1 mg to about 100 mgpyridoxine; from about 1 mg to about 100 mg calcium pantothenate; fromabout 100 μg to about 500 μg cyanobalamin; from about 1 mg to about 20mg Zn; from about 1 mg to about 100 mg Se; from about 1 mg to about 1000mg Cu; from about 0.01 mg to about 10 mg Mn; and from about 1 mg toabout 20 mg Fe. In another preferred aspect of the invention, themagnetic dipole stabilized solution comprises about 395 mg sodiumascorbate; about 255 mg magnesium chloride 2H₂O; about 200 mg2-di-methyl amino ethanol HCl; about 36 mg thiamine; about 7.3 mgriboflavine; about 100 mg nicotinamide; about 18.2 mg pyridoxine; about18.2 mg calcium pantothenate; about 320 μg cyanobalamin; about 10 mg Zn;about 45 mg Se; about 400 mg Cu; about 0.3 mg Mn; about 8 mg Fe; andelectroactivated water.

In a different embodiment, the invention provides a kit comprising afirst vial containing a solution comprising vitamins, salts, acids,vitamers, or mixtures thereof, and a second vial containing a magneticdipole stabilized solution comprising electroactivated water.Preferably, the kit comprises instructions for use. In a preferredaspect of the invention, the magnetic dipole stabilized solution has apositive electrical potential before mixing the contents of the vials.In an even more preferred aspect of the invention, the magnetic dipolestabilized solution has a negative electrical potential after combiningthe first and second vials. Preferably, the solution in the first vialcomprises sodium ascorbate, magnesium chloride 2 H₂O, 2 di-methyl aminoethanol HCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate, and cyanobalamin.

In another embodiment, the invention provides a kit comprising a firstvial containing a magnetic dipole stabilized solution comprisingelectroactivated water and one or more selected from the groupconsisting of heparin, vitamins, salts, acids, lipoic acid, folic acid,antibiotic(s) and vitamers, and mixtures thereof; a second vialcontaining a magnetic dipole stabilized solution; and instructions foruse. In a preferred aspect of the invention, the solution in the firstvial comprises lipoic acid in an amount of between about 10 mg and 500mg. Preferably, the amount of lipoic acid is between about 100 mg and400 mg. Even more preferably, the amount of lipoic acid is about 250 mg.In another preferred aspect of the invention, the solution in the firstvial comprises sodium ascorbate, magnesium chloride 2H₂O, 2 di-methylamino ethanol HCl, thiamine, riboflavine, nicotinamide, pyridoxine,calcium pantothenate, cyanobalamin, lipoic acid, folic acid, andantibiotic(s).

DETAILED DESCRIPTION

The present invention will now be described more fully hereinafter.However, many modifications and other embodiments of the presentinvention set forth herein will come to mind to one skilled in the artto which the invention pertains having the benefit of the teachingspresented in the foregoing descriptions. Therefore, it is to beunderstood that the present invention is not to be limited to thespecific embodiments disclosed and that modifications and otherembodiments are intended to be included within the scope of the appendedclaims.

Methods of treating or ameliorating skin conditions, diabeticconditions, cardiovascular conditions, cancer and infections byadministering a magnetic dipole stabilized solution (MDSS) are provided.Also provided are methods of chelating, reducing the amount of metal ina mammal, increasing the amount of excretion of metal from a mammal,enhancing performance and nutritional supplementation by administering amagnetic dipole stabilized solution (MOSS). The MDSS compositions hereinpossess properties that when administered to a subject in need thereofprovide a therapeutic or cosmetic effect for the skin, enhanceperformance or nutritional support, treat or ameliorate diabeticconditions, cardiovascular conditions, cancer and infections, providechelation, reduce the amount of metal in a subject and increase metalexcretion from a subject. Among other properties, the compositions arecapable of restoring cellular integrity and transmembrane potential,modulating cellular membrane permeability and enhancing the transfer ofmolecules and ions through the cell membranes. Data provided herein showthat these properties have a beneficial result when administered to asubject for the conditions described herein. Surprisingly, the MDSScompositions comprising vitamins or other ingredients described hereinare very effective even for conditions that have not responded to priortreatments. Because the MDSS compositions are safe and non-toxic, theycan be administered prophylactically to prevent or reduce the likelihoodof onset of the conditions or symptoms described herein. One example isadministration of an MDSS composition subsequent to exposure to asubstance that may lead to an increased risk of increased metal in thebody.

The purpose of the chelating agent is, of course, to sequester metals,such as paramagnetic metals, heavy metals or radionuclides. Heavy metalsinclude toxic metals and elements that exhibit metallic properties,which would mainly include the transition metals, some metalloids,lanthanides, and actinides. Suitable metals include calcium, aluminum,beryllium, cadmium, copper iron, lead, uranium, plutonium, arsenic andmercury. Other suitable paramagnetic metals include a lanthanide elementof atomic numbers 58-70 or a transition metal of atomic numbers 21-29,42 or 44, such as scandium, titanium, vanadium, chromium, manganese,iron, cobalt, nickel, copper, molybdenum, ruthenium, cerium,praseodymium, neodymium, promethium, samarium, europium, gadolinium,terbium, dysprosium, holmium, erbium, thulium, and ytterbium, mostpreferably Gd(III), Mn(II), iron, europium and/or dysprosium. Suitableradionuclides include the radioactive forms of, for example, Sm, Ho, Y,Pm, Gd, La, Lu, Yb, Sc, Pr, Tc, Re, Ru, Rh, Pd, Pt, Cu, Au, Ga, In, Sn,and Pb.

As used herein, the term “metal poisoning” refers to an excessivebuild-up of a particular metal in the mammal. The symptoms of metalpoisoning are well known and differ depending on the particular metaland the mammal. A mammal can be asymptomatic but nevertheless besuffering from metal poisoning.

As used herein the term “mammal” refers to humans as well as all othermammalian animals. As used herein, the term “mammal” includes a“subject” or “patient” and refers to a warm blooded animal. It isunderstood that guinea pigs, dogs, cats, rats, mice, horses, goats,cattle, sheep, zoo animals, livestock, primates, and humans are allexamples of animals within the scope of the meaning of the term. As usedherein “a mammal in need thereof” may be a subject whom could have beenbut is not required to have been diagnosed as suffering from thecondition intended to be treated. In one aspect, the present method isdirected to conditions that are noticeable to the subject and thesubject wishes to treat or ameliorate the condition without a formaldiagnosis. For instance, a subject wishing to ameliorate alopecia is asubject who has hair loss or wishes to stave off subsequent hair loss.In another example, a subject with acne does not necessarily need to bediagnosed to know that he or she has acne. Alternatively, a subjectcould be diagnosed with a skin condition and seek treatment oramelioration by a method disclosed herein. Clearly, one who suffers fromthese conditions has an acute awareness of the problem with or without aformal diagnosis by medical personnel. Alternatively, one may be awareof symptoms associated with metal poisoning without knowing that metalpoisoning may be causing the symptoms. One may wish to have chelationtreatment to improve or ameliorate the symptoms. In other words, amammal, if human, in need of being treated can appreciate the purposefor which he or she is being treated, whether it is to treat a symptomof a known or unknown cause or the underlying cause with or withoutformal diagnosis. Alternatively, a mammal in need thereof is one who hasbeen diagnosed as having a condition and is in need of specifictreatment.

As used herein the terms “treating” and “ameliorating” are intended torefer to all processes wherein there may be a slowing, interrupting,arresting, or stopping of the progression of the condition or symptomsand does not necessarily indicate a total elimination of the underlyingcondition. The terms also encompass the administration of a MDSScomposition wherein the mammal has a condition or symptom or apredisposition towards a condition or symptom, where the purpose is tocure, heal, alleviate, relieve, alter, improve or affect the conditionor symptom or the predisposition to the same. Also contemplated ispreventing the condition or symptom or the predisposition to the same byprophylactically administering a MDSS composition as described herein.

As used herein, the term “skin condition” means a disorder, disease orsymptom related to the skin. The term “skin” is meant to describe theouter covering of a mammalian form including, without limitation, theepidermis, dermis, and subcutaneous tissues. The skin can include othercomponents such as hair follicles and sweat glands. A number of skinconditions can be treated according to the methods of the presentinvention and include skin disorders of the hair follicles and sebaceousglands. These and other conditions include, but are not limited to,intrinsic skin aging, wrinkles, acne, photodamage, rosacea, scars,hypertrophic scars, keliods, stretch marks or Striae distensae,psoriasis, nutrient status, anti-oxidant status, energy status, oxygenstatus, eicosanoid staus, leukotriene status, pruritus, ehlers-danlossyndrome, scleroderm a, post inflammatory hyperpigmentation, melasma,alopecia, poikiloderma of civatte, viteligo, skin cancers, skindyschromas, or blotchy pigmentation. Preferably, skin conditions such asacne, alopecia and burns among others, can be treated according to thepresent invention. The skin consists in the widest organ existing in thehuman body. Among the functionalized structures present therein, thevascular system, lymphatic system, glands and nerves, are detached.Interaction of all its structures in an orderly manner, confers to theskin a fundamental role on existence and survival of the livings,constituting an efficient interface between external ambient andinternal organs, which main function is to protect from water loss,contingent intruders, strange material, pathogenic organisms andmicroorganisms. Further to these functions, skin is able to eliminate aseries of catabolites originating from internal biochemical processesand to maintain the ideal temperature constant for the adequatefunctioning of living organisms.

Skin is structurally composed of two tissue layers. The epidermis is themost external layer. It is constituted of a series of epitheliumstratified cell layers, which quantity of keratin protein proportionallyincreases on most external layers. This arrangement makes the mostexternal layers more compact, offering greater protection in relation toexcessive water loss, action of strange substances and organisms,besides offering greater resistance to abrasion and injuries. This layerdoes not contain any blood vessel and is sustained by fluids of thelayer immediately beneath the dermis, this one presenting irregularconnection arrangements, presenting more complex tissues and containingblood vessels between a series of specialized structures.

Skin integrity can eventually be ruptured, causing a series of problemswith reference to maintenance of the internal functions of the organism.This rupture can occur due to perforations, accidental or programmedcuts (surgeries), burns, injuries resulting from degenerating processes,having diseases, congenital anomalies or alterations of biochemicalprocesses as a cause, resulting in ulceration, among others.

Under normal conditions, the body has mechanisms to repair andeventually recover, partial or totally, several skin ruptures, in orderto restore its integrity and functionality. This repair process isdirectly related with rupture extension, tissues affected, injury andpatient physical condition. Contamination of exposed tissue by strangesubstances and live organisms will be another factor that will influenceon the mechanism and the velocity of the repair process. Skin healingprocess involves particular groups of cells and proteins in a complexbiochemical mechanism. This renovation process is generally divided inthree temporary phases known as inflammation, proliferation andremodeling.

At the initial stage of inflammation, the platelets present out of thecirculatory system become more active, producing aggregation. Thus, theysignalize the beginning of the repair process, forming a set oftemporary cells to avoid hemorrhage and prevent bacterial invasion.Blood vessels under growth, infiltrates in the affected site,discharging various mediator molecules, including other plateletsresulting from growth factors, Willibrand factor, thrombospondine,fibronectine, fibrinogen, 5-hydroxytriptophan, thromboxane-A2 andadenosine diphosphate (Kirsner e Eaglstein, J. Dermatol. 151:629-640,1993). The set of cells that characterizes the clotting are bonded andprovides a matrix of monocytes, fibroblasts and keratinocytes.Chemostatic molecules attract the monocytes that are transformed intomacrophages and secreting additional growth factors (Nathan e Sporn. J.Cell Biol. 113:981-986, 1991). Neutrophyls can assist these processessecreting degrading enzymes, the elastases and collagenases, increasingthe passage through the basis of cellular membrane. The most importantrole of the neutrophyls seems to be cleaning the affected tissue ordefend the area from contingent intruders, accelerating the process as awhole, removing the dead cells and platelets. Infiltration ofneutrophyls ceases within 48 hours approximately, provided that nobacterial contamination occurs. The neutrophyls excess is phagocyted bymacrophages resulting from monocytes of the circulatory system. It isbelieved that the macrophages are essential for an efficient recoveryprocess, also being responsible for the phagocytes process of pathogenicorganisms and for the cleaning of other materials strange to the body.Moreover, they deliver innumerous factors involved in subsequent eventsin tissue recovery process.

The second recovery stage, the proliferation, generally begins 48 hoursafter occurring tissue injury. Fibroblasts begin to proliferate andmigrate to the interior of affected space, starting from the alreadybond tissues and reaching the end of injury. Fibroblasts yield collagenand glycosaminoglycans, stimulating a proliferation of endothelialcells. Endothelial cells will promote the growth of a new net of bloodvessels. Collagenases and plasminogen activators are secreted fromkeratinocytes. If the recovery process is not disturbed, an adequatesupply of nutrients with oxygen, the keratinocytes can migrate to theaffected tissue. It is believed that keratinocytes only migrate on livetissues and, as a consequence, keratinocytes migrate through areasbeneath dead tissues and in interface between the affected area and thatalready recovered. Angiogenesis, formation of new blood vessels inresponse to chemotactic signals (Folkman and Klagsbrun, Science235:442-447, 1987), and fibroplasias, accumulation of fibroblasts andformation of tissues granulation, also occur during the proliferatingphase.

The third and last recovery stage, the remodeling, starts when theepithelium is already recovered. In this phase, which can be extendedfor many years, the affected tissue obtains its normal strength, slowlyundergoing structural readjustments, always on account of depth, as wellas the extension of the affected area. Remodeling of tissues is followedby the secretion of cellular matrix components, including fibronectine,collagen and proteoglycan, which serve as a support for the cellularmigration and for the tissue. The type III collagen, synthesized at theinitial stages of the recovery process, is substituted by type Icollagen, the most permanent form, by a response proteolitic process.The affected surface is subsequently coated with an enlargement process,making the surface smoother. These epithelial cells are spread at layersunderneath the unstructured area, in order that the affected layers andthose above it are slowly substituted or recovered.

This complex process of natural regeneration takes considerable time andcan be affected by pathological conditions as infections, maceration,dry skin and overall patient health. This can lead to chronic ulcerformation, making this process still slower. Other severe conditions canbe established in tissues regeneration course. Ischemia, for example,refers to a pathological condition resulting from a located dysfunctionof the vascular system, resulting in inadequate blood supply withsubsequent damage to the affected cellular tissue.

The term “acne” is meant to include any skin condition where a skin porebecomes blocked and/or thereby becomes inflamed. The term acne includeswithout limitation superficial acne, including comedones, inflamedpapules, superficial cysts, and pustules; and deep acne, including deepinflamed modules and pus-filled cysts. Specific acne conditions caninclude, but are not limited to, acne vulgaris, acne comedo, papularacne, premenstrual acne, preadolescent acne, acne venenata, acnecosmetica, pomade acne, acne detergicans, acne excoriee, gram negativeacne, acne rosacea, pseudofolliculitis barbae, folliculitis, perioraldermatitis, and hiddradenitis suppurativa. Acne is a common inflammatorypilosebaceous disease characterized by comedones, papules, pustules,inflamed nodules, superficial pus-filled cysts, and (in extreme cases)canalizing and deep, inflamed, sometimes purulent sacs. Acne involves aninteraction between hormones, keratinization, sebum, and bacteria thatsomehow determines the course and severity of acne. It often begins atpuberty, when the increase in androgens causes an increase in the sizeand activity of the pilosebaceous glands. The earliest microscopicchange is thought to be intrafollicular hyperkeratosis, which leads toblockage of the pilosebaceous follicle with consequent formation of thecomedo, composed of sebum, keratin, and microorganisms, particularlyPropionibacterium acnes. Lipases from P. acnes break down triglyceridesin the sebum to form free fatty acids (FFA), which irritate thefollicular wall. Retention of sebaceous secretions and dilation of thefollicle may lead to cyst formation.

Skin conditions also include, but are not limited to, dermatologicalconditions linked to disorders of keratinization involvingdifferentiation and proliferation, in particular, acne vulgaris,comedonic or polymorphic acne, nodulocystic acne, acne conglobata,senile acne and secondary acnes such as solar, drug or occupationalacne; for other types of keratinization disorders especially ichthyoses,ichthyosiform conditions, Darier's disease, palmoplantar keratoderma,leukoplakia and luecoplakiform conditions or lichen and lichen planus;dermatological disorders having an inflammatory or immunoallergiccomponent, in particular, all forms of psoriases, either cutaneous,mucosal or ungual, and psoriatic rheumatism, and cutaneous atopy such aseczema or respiratory atopy, dry skin, inflammation of the skin, solarerythema, skin allergies or other skin disorders of the epidermis anddermis.

Psoriasis is a skin condition characterized by hyperplasia ofkeratinocytes resulting in thickening of the epidermis and the presenceof red scaly plaques. The lesions in this chronic disease typically aresubject to remissions and exacerbations. There are several patterns, ofwhich plaque psoriasis is the most common. Guttate psoriasis, withraindrop shaped lesions scattered on the trunk and limbs, is the mostfrequent form in children, while pustular psoriasis is usually localizedto the palms and soles. The classical inflammatory lesions vary fromdiscrete erythematous papules and plaques covered with silvery scales,to scaly itching patches that bleed when the scales are removed.Psoriasis is a condition in which cell proliferation is increased up to10 times the normal rate for an individual. The skin is the largestportion of the human body which is comprised of cells within three skinlayers. Each of the skin layers is in a constant state of growth withthe outer layer being formed of predominantly dead tissue which isnaturally being discarded at a normal rate. Replacement of cells fromunderlying layers is accomplished by cell division and maturation wherecells move upwardly and outwardly at a rate which varies dependent uponthe age, sex, and/or health of an individual. Psoriasis causes anincreased turnover of cells, which in turn increases the rate of cellgrowth and cell death. This increased rate of cell growth and cell deathmay result in injuries and/or disorders which accompany the increasedsynthesis of all tissue components and further elevate the strain placedupon skin or other tissue and the bio-synthetic capabilities of thecells within the affected area.

The terms eczema and dermatitis are generally used names for severeinflammation of the skin, usually with redness, swelling, oozing,rusting or scaling of lesions which are usually itchy. Eczema may takethe form of contact dermatitis (due to skin contact with the cause) oratopic dermatitis in individuals who are “atopic” or allergic by nature.If the scalp is involved the disorder is known as seborrheic dermatitis.Dermatitis can be caused by chemicals, plants, shoes, clothing, metalcompounds and even medicines used to treat dermatitis. In atopicdermatitis environmental temperature, humidity changes, bacterial skininfections, airborne allergens and garments, e.g., wool, may all bringabout dermatitis.

Alopecia is a skin condition that results in the loss of hair on thescalp and elsewhere. It usually starts with one or more small, round,smooth patches and occurs in males and females of all ages. Loss of hairin one or several small spots is common, but it is possible to lose allscalp hair (alopecia totalis), or every hair on the body (alopeciauniversalis), which is rare.

The skin condition, rosacea is of an unknown origin. It usually affectsthe middle third of the face causing skin redness, prominentvascularization, papules, pustules and swelling, as well as apredisposition to flushing and blushing. However, rosacea can also occuron other parts of the body including the chest, neck, back, or scalp.The blood vessels near the skin dilate and become more visible therethrough, resulting in telangiectasia. The resulting papules and pustulesresemble teenage acne, and are frequently mistaken for the same. Unlikeacne, rosacea does not have blackheads or whiteheads. Rosacea, however,can occur in all age groups and in both sexes, where it tends to be morefrequent in women but more severe in men. The flushing and blushingregions of the face are affected by rosacea. Emotional factors such asanxiety, embarrassment, or stress may evoke or aggravate rosacea. Inaddition, a flare-up may be caused by environmental or climatevariances, and UV exposure is known to aggravate rosacea. Furthermore,diet is also known to aggravate rosacea. Spicy foods, alcoholicbeverages, hot beverages, and smoking are known to cause flare-ups.Rosacea is not only an aesthetic complication. Rosacea is a chronicdisease that has rarely been documented to reverse its progression. Ifuntreated, the condition worsens and spreads. Untreated rosacea maycause a disfiguring nose condition called rhinophyma, which ischaracterized by a bulbous, red nose and inflamed cheeks. Severerhinophyma may require surgery, an invasive procedure that may beavoided by timely treatment. Another problem of advanced rosacea isocular. Persons afflicted with rosacea may experience conjunctivitis, aburning and grittiness of the eyes. If untreated, it may lead to seriouscomplications such as rosacea keratitis, which damages the cornea andmay impair vision.

Burns involve a type of skin integrity rupture. Burns represent one ofthe most painful processes that can be established in this tissue,needing the establishment of a coordinated therapy to help its recoveryand pain treatment. Burns can be caused by several factors, among which,exposure to high or low temperatures, exposure to chemical compounds, byelectricity, by exposure to radiation and mechanical friction. Burnseverity and its risk are evaluated according to the amount of affectedtissue and depth reached. The amount of affected tissue is representedby the percentage of burned corporeal surface (BCS). In this type ofevaluation, burns can be divided into small, moderate, large or massiveburns, where regions inferior to 15% of BCS, from 15% up to 49% of BCS,from 50% up to 69% of BCS and over 70% of BCS, respectively. Theextension of the affected area is determined through Lund-Browderscheme, which takes into consideration the burn proportion, inaccordance with the age of the burned patient. Another rule that is mostused for determining the extension of the affected area is that known asWallace Rule or Rule of Nines, a technique less efficient than theforegoing, however, easy to memorize, being very much employed inemergency cases. This rule applies a value equaling nine or ninemultiple to the affected parts, being 9% for each superior member, 9%for the head, 18% for each inferior member, 18% for each torso face and1% for the genitalia.

The classification as first, second and third degree corresponds to burndepth. The first-degree injury corresponds to the burn that affects theskin most external layer (epidermis), not producing hemodynamicalterations, however the affected region is found hyperemic in absenceof blisters or phlyctenae. This type of injury can be observed inerythemae resulting from sunrays or heated water. The second-degreeinjury affects either the epidermis as part of the dermis and is mainlycharacterized by the formation of blisters or phlyctenae, as thoseresulting from scalding or thermal injury resulting from overheatedliquid. The third-degree injury endangers the totality of skin layers(epidermis and dermis) and, in many cases, can affect other tissues, asthe subcutaneous cellular tissue, muscular tissue and bone tissue.Third-degree burns are considered as the most severe of all thermalinjuries, producing deforming injuries. For being deeper, it eliminatesthe nerve endings responsible for shooting the painful message. Thesetypes of burns need transplanting for recomposing destroyed tissues,since the structures and organelles necessary for the natural recoveryprocess, were eliminated. Since burns are wounds that involve the skin,they develop afore mentioned complex process of regeneration andrecomposition of injured tissue. The speed or grade of re-epithelizationof the affected region is small the greater the area involved is,considerably increasing the recovery time, when the injuries start tocover a body surface over 10% or 15%.

Immediately after the burn trauma, an inflammatory process developswherein various agents are delivered, occurring deposition of fibrinsand platelets activated on the wound surface. A matrix rich in organicmaterial is yielded, able to enclosure bacteria and other strangesubstances, which frequently aggravates the case, due to sepsis that canfollow trauma. During this inflammatory process a great quantity ofexudates crop out of the burned region, leading the patient to anintense loss of liquids, which, depending on the burn extension anddepth, can cause a severe dehydration case. The inflammatory processextends to adjacent tissues, factor that endangers the functions ofthese tissues initially intact.

Extensive and deep burns cause alterations that are extended far beyondthe affected local, such as anatomic, metabolic, physiological,endocrinology and immune alterations, requiring special care.Significant fluid losses, delivery of inflammatory multi-mediators andcontamination by bacteria, occur. When disseminated in central organsthrough circulation, bacteria and inflammatory mediators can causecardiac endangerment, failure of gastrointestinal mucous integrity andin extreme cases, multi-organic failure.

Hemodynamic alterations that occur after severe thermal injuries includedecrease of cardiac output and reduced volume of circulating plasma,contributing all to a hypovolemic shock. Inflammatory mediators(including cytokines, prostaglandin, nitric oxide and superoxide ions)have been implicated in causing further damage to tissues. It isbelieved that despite local benefit, such mediators induce undesirableeffects when reaching significantly high levels. As an example, agreater damage to tissues can be caused by delivery of proteoliticenzymes and superoxide ions of macrophages and activated leucocytes.

Thus, burns are skin conditions that develop unbalance in a series ofnatural organic mechanisms, not limited to endangered tissues only, butinvolve numerous organs that can be affected. Additionally, largethermal injuries induce to a sharp increase in basal metabolic rate.Large nitrogen corporeal losses, observed in burned patients, mainlyoccur due to protein exudation through burned skin and also by the factthat, under such catabolic stress situation, corporeal proteins canbecome the metabolic substrate used for production of 15 to 20% of totalenergy required by the organism. Further to these abnormalities,hormonal levels change with an increase in cathecolamines, cortisol andglucagons, in the presence of normal or slightly increased levels ofinsulin. These hormonal alterations promote increase of proteolysis andlipolysis. Thus, the entire complex process is characterized byimbalance. The quick recovery of the skin of a burned mammal is ofutmost importance for recovery of his normal organic functions.

Other skin conditions can include dry/chapped skin. Thus, the methodsdisclosed herein are useful for treating or ameliorating the skinagainst the effects of environmental conditions.

As used herein, a “condition associated with diabetes” includes obesity,hypertension, hyperlipidemia, fatty liver disease, nephropathy,neuropathy, renal failure, retinopathy, diabetic ulcer, cataracts,insulin resistance syndromes and cachexia. Diabetic diseases andconditions that are especially suited for treating or ameliorating witha MDSS composition as described herein are ulcers.

As used herein, “cardiovascular dysfunction” includes conditions anddiseases such as coronary heart disease, cerebrovascular disease,hypertension, peripheral artery disease, occlusive arterial disease,angina, rheumatic heart disease, congenital heart disease, heartfailure, cardiac insufficiency, palpitations, supraventriculartachycardia, fibrillation, faintness, dizziness, fatigue, migraine, highlevels of total blood cholesterol and/or LDL cholesterol, low level ofHDL cholesterol, high level of lipoprotein, infections of the heart suchas carditis and endocarditis, diabetic ulcer, thrombophlebitis, Raynaudsdisease, claudication and gangrene. Diseases and conditions that areespecially suited for treating or ameliorating with a MDSS compositionas described herein are peripheral artery disease and atherosclerosis.

As used herein, the term “cancer” refers to a physiological condition inmammals that is typically characterized by unregulated cellgrowth/proliferation. Examples of cancer include but are not limited to,carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More particularexamples of such cancers include adrenocortical cancer; bladder cancer;bone cancer; brain cancer; breast cancer; cancer of the peritoneum;cervical cancer; colon cancer; colorectal cancer; endometrial or uterinecarcinoma; esophogeal cancer; eye cancer; gallbladder cancer;gastrointestinal cancer; glioblastoma; various types of head and neckcancer; hepatic carcinoma; hepatocellular cancer; kidney cancer;laryngeal cancer; liver cancer; lung cancer, such as, for example,adenocarcinoma of the lung, small-cell lung cancer, squamous carcinomaof the lung, non-small cell lung cancer; melanoma and nonmelanoma skincancer; myeloproliferative disorders, such as, for example, polycythemiavera, essential thrombocythemia, chronic idiopathic myelofibrosis,myeloid metaplasia with myelofibrosis, chronic myeloid leukemia (CML),chronic myelomonocytic leukemia, chronic eosinophilic leukemia,hypereosinophilic syndrome, systematic mast cell disease, atypical CML,or juvenile myelomonocytic leukemia; ovarian cancer; pancreatic cancer;prostate cancer, including benign prostatic hyperplasia; rectal cancer;salivary gland carcinoma; squamous cell cancer; testicular cancer;thyroid cancer; and vulval cancer. Also contemplated is the use of aMDSS composition as an adjuvant to a primary therapy against one of theabove-listed cancers. A cancer can be treated or ameliorated by treatingor ameliorating a symptom of the cancer or secondary conditions of thecancer.

As used herein, the term “anti-infective” includes antiviral orantibiotic or any biostatic activity, i.e., where the proliferation ofthe target species is reduced or eliminated, and true biocidal activitywhere the target species are killed. Furthermore, the terms “microbe” or“antimicrobial” should be interpreted to specifically encompass bacteriaand fungi as well as other single-celled organisms such as mold, mildewand algae. In this embodiment, it is preferred that the compositionfurther comprise an antibiotic. The antibiotic can be an antibioticeffective against bacteria, including gram-negative and gram-positiveorganisms. Antibiotics include tetracycline, oxytetracycline,metacycline, doxycycline, minocycline, erythromycin, lincomycin,penicillin G, clindamycin, kanamycin, chloramphenicol, fradiomycin,streptomycin, norfloxacin, ciprofloxacin, ofloxacin, grepafloxacin,levofloxacin, sparfloxacin, ampicillin, carbenicillin, methicillin,cephalosporins, vancomycin, bacitracin, gentamycin, fusidic acid,ciprofloxin and other quinolones, erythromycin, gentamicin,sulfonamides, trimethoprim, dapsone, isoniazid, teicoplanin, avoparcin,synercid, virginiamycin, piperacillin, ticarcillin, cefepime, cefpirome,rifampicin, pyrazinamide, enrofloxacin, amikacin, netilmycin, imipenem,meropenem, inezolidcefuroxime, ceftriaxone, cefadroxil, cefazoline,ceftazidime, cefotaxime, roxithromycin, cefaclor, cefalexin, cefoxitin,amoxicillin, co-amoxiclav, mupirocin, cloxacillin, co-trimoxazole,pharmaceutically acceptable salts thereof, derivatives thereof, andcombinations thereof. Especially preferred agents are erythromycin andgentamicin. The MDSS composition could alternatively or in addition toinclude one or more antiviral, antiseptic or antimicrobial agents.

As used herein, the term “metal poisoning” refers to an excessivebuild-up of a particular metal in a subject. The symptoms of metalpoisoning are well known and differ depending on the particular metaland the subject. A subject can be asymptomatic but nevertheless besuffering from metal poisoning.

“Athletic performance” refers to any professional or recreationalactivity wherein the performer, for example an athlete, exerts aphysical act, such as running, swimming, golf, bowling, archery,football, baseball, basketball, soccer, hiking, cycling, dancing and thelike. “Cognitive performance” refers to any activity wherein theperformer exerts a mental act and can include test-taking, focusing,concentrating, memorizing, studying and the like. A general state of“alertness” refers to the ability to focus or concentrate on a giventask or performance. Alertness then can be viewed as an ability to staveoff fatigue, mental tiredness or decreasing cognitive performance, suchas when driving, boating, operating equipment, piloting, speech making,monitoring, police or security work, attending seminars and classes,working and the like. The magnetic dipole stabilized solutioncompositions described herein can be administered preferably before, butalso during, long-lasting sports activities, any time an energetic boostis desired or when maintenance of energy levels is desired.

As used herein, the term “nutrition support” is intended to mean acomposition that provides beneficial components that can includenutrients. The beneficial components are intended to work in conjunctionwith a separate primary nutrient source to meet the dietary needs of amammal.

As used herein, the term “special dietary needs” refers to any mammalthat has a restricted diet. The diet may be restricted because ofallergy, but also because an unrestricted diet would likely cause themammal to develop a food-borne condition. For example, the etiology of anumber of gastrointestinal conditions is caused by the reaction towardscertain foods in certain mammals. Subjects who are nauseous are alsolikely to have special diets in order to maintain a healthy nutrition.An example of this is cancer chemotherapy patients or AIDS patients.These individuals have difficulty maintaining an appetite or may besuffering from cachexia. Often children do not have appetites forvarious reasons and thus sometimes require a special diet to meetdietary needs. Individuals who are unconscious for long periods of time,for instance comatose patients will require special feeding solutions tomaintain nutrition. The magnetic dipole stabilized solutions describedherein can be useful adjuvants for helping to maintain dietary needs insituations such as these.

As used herein the term “enhancing performance” is intended to mean anyimprovement in performance. Performance can be assessed in any manner.Certain enhancements are readily measured. For example, in atimed-event, an improved time can assess an enhanced performance.Certain performance enhancing properties can be judged subjectively bythe athlete or performer or an observer. In these instances, an enhancedperformance means that the performance was perceived subjectively to beimproved, magnified, faster, better and the like. The compositionsdescribed herein are effective for enhancing performance without theside effects of conventional stimulating agents such as caffeine orother substances banned from athletic competition or substances that amammal cannot tolerate ingesting because of nausea or other conditions.Performance can be an athletic performance, a cognitive performance or ageneral state of alertness.

Thus, in one embodiment, the invention is directed to a method oftreating or ameliorating a skin condition, a condition associated withdiabetes, a condition associated with a cardiovascular dysfunction, acancer, an infection, or metal poisoning in a subject in need thereof,or reducing the amount of metal in a subject in need thereof, orincreasing metal excretion from a subject in need thereof, or enhancingperformance of a subject or providing nutrition support to a subject inneed thereof, comprising administering to the subject by injection amagnetic dipole stabilized solution composition. In a preferred aspectof the invention, the magnetic dipole stabilized solution comprisessodium ascorbate, magnesium chloride 2H₂O, 2-di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate cyanobalamin, and electroactivated water. In a preferredaspect, the magnetic dipole stabilized solution comprises from about 100mg to about 500 mg sodium ascorbate, from about 100 mg to about 500 mgmagnesium chloride 2H₂O, from about 100 mg to about 500 mg 2 di-methylamino ethanol HCl, from about 1 mg to about 100 mg thiamine, from about1 mg to about 100 mg riboflavine, from about 1 mg to about 300 mgnicotinamide, from about 1 mg to about 100 mg pyridoxine, from about 1mg to about 100 mg calcium pantothenate, from about 100 μg to about 500μg cyanobalamin, and electroactivated water. In another preferred aspectof the invention, the magnetic dipole stabilized solution furthercomprises folic acid and/or an antibiotic. In one aspect of theinvention, the treatment or amelioration of a skin condition comprisescontacting the skin area to be treated or ameliorated with the solution.In a different aspect of the invention, the magnetic dipole stabilizedsolution used for the treatment or prevention of cancer furthercomprises vitamin K2.

In another embodiment, the invention is directed to a method of treatingor ameliorating a skin condition that is an infection, comprisingadministering to a subject by injection a magnetic dipole stabilizedsolution, wherein the infection is treated or ameliorated. In thisregard the method can be said to be an anti-infective treatment. In apreferred embodiment, the magnetic dipole stabilized solution compriseselectroactivated water. The magnetic dipole stabilized solution forinjection preferably has a negative or neutral electric potential.

In another embodiment, the present disclosure is directed to a method oftreating or ameliorating a skin condition, a condition associated withdiabetes, a condition associated with a cardiovascular dysfunction, acancer, an infection, or metal poisoning in a subject in need thereof,or reducing the amount of metal in a subject in need thereof, orincreasing metal excretion from a subject in need thereof, or enhancingperformance of a subject or providing nutrition support to a subject inneed thereof, comprising administering to a subject in need thereof byinjection a magnetic dipole stabilized solution composition comprising,sodium ascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate, cyanobalamin, lipoic acid and electroactivated water. Thesolution may further include folic acid and/or an antibiotic.

In another embodiment, the present invention is directed to a method oftreating or ameliorating a skin condition, a condition associated withdiabetes, a condition associated with a cardiovascular dysfunction, acancer, an infection, or metal poisoning in a subject in need thereof,or reducing the amount of metal in a subject in need thereof, orincreasing metal excretion from a subject in need thereof, or enhancingperformance of a subject or providing nutrition support to a subject inneed thereof, comprising administering to a subject in need thereof byinjection a magnetic dipole stabilized solution composition comprising,sodium ascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate, cyanobalamin, lipoic acid, folic acid and electroactivatedwater. The solution may further include an antibiotic.

In another embodiment, the present invention is directed to a method oftreating or ameliorating a skin condition, a condition associated withdiabetes, a condition associated with a cardiovascular dysfunction, acancer, an infection, or metal poisoning in a subject in need thereof,or reducing the amount of metal in a subject in need thereof, orincreasing metal excretion from a subject in need thereof, or enhancingperformance of a subject or providing nutrition support to a subject inneed thereof, comprising administering to a subject in need thereof byinjection a magnetic dipole stabilized solution composition comprising,sodium ascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate, cyanobalamin, lipoic acid, folic acid, one or moreantibiotics and electroactivated water.

In another embodiment, the present subject matter is directed to acomposition for treating or ameliorating diseases comprising sodiumascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanol HCl,thiamine, riboflavine, nicotinamide, pyridoxine, calcium pantothenate,cyanobalamin and electroactivated water. The composition may furtherinclude lipoic acid, folic acid and/or one or more antibiotics.

Preferably, sodium ascorbate is present in an amount equivalent toascorbic acid from about 0.01 g to about 10 g per dose (preferably in a10 ml dose). Preferably, the amount is from about 0.1 g to about 1.0 gper dose. More preferably, the amount is from about 0.24 g to about 0.9g per dose.

Preferably, magnesium chloride is present in an amount from about 0.01 gto about 10 g per dose (preferably in a 10 ml dose). Preferably, theamount is from about 0.1 g to about 1.0 g per dose. More preferably, theamount is from about 0.5 g to about 0.8 g per dose.

Preferably, dimethyl amino ethanol HCl, is present in an amount fromabout 0.01 g to about 10 g per dose (preferably in a 10 ml dose). Morepreferably, the amount is from about 0.1 g to about 1.0 g per dose. Evenmore preferably, the amount is from about 0.2 g to about 0.87 g perdose.

Preferably, thiamine is present in an amount from about 0.01 g to about10 g per dose (preferably in a 10 ml dose). More preferably, the amountis from about 0.1 g to about 1.0 g per dose. Even more preferably, theamount is from about 0.12 g to about 0.15 g per dose.

Preferably, riboflavin is present in an amount from about 0.001 g toabout 1.0 g per dose (preferably in a 10 ml dose). More preferably, theamount is from about 0.01 g to about 1.0 g per dose. Even morepreferably, the amount is from about 0.01 g to about 0.02 g per dose.

Preferably, nicotinamide is present in an amount from about 0.01 g toabout 10 g per dose (preferably in a 10 ml dose). More preferably, theamount is from about 0.1 g to about 1.0 g per dose. Even morepreferably, the amount is from about 0.10 g to about 0.15 g per dose.

Preferably, pyridoxine is present in an amount from about 0.01 g toabout 10 g per dose (preferably in a 10 ml dose). More preferably, theamount is from about 0.1 g to about 1.0 g per dose. Even morepreferably, the amount is from about 0.55 g to about 0.65 g per dose.

Preferably, calcium pantothenate is present in an amount from about0.001 g to about 1.0 g per dose (preferably in a 10 ml dose). Morepreferably, the amount is from about 0.01 g to about 1.0 g per dose.Even more preferably, the amount is from about 0.03 g to about 0.04 gper dose.

Preferably, cyanobalamin is present in an amount from about 0.1 g toabout 10 g per dose (preferably in a 10 ml dose). More preferably, theamount is from about 1 g to about 5 g per dose. Even more preferably,the amount is from about 1.8 g to about 2.25 g per dose.

Preferably, vitamin K2 is present in an amount from about 0.01 mg to 125mg per dose (preferably in a 10 ml dose), including about 1 mg, about 5mg, about 20 mg, about 50 mg, about 75 mg and about 100 mg per dose.

When lipoic acid, its salts or mixtures thereof are present, the amountof lipoic acid is preferably from about 10 mg to about 500 mg. Alsopreferred is an amount from about 100 mg to about 400 mg. Morepreferably, the amount is from about 250 mg to about 350 mg. Mostpreferably, the amount is about 250 mg. Solubility modifiers including,but not limited to, emulsifying agents such as phosphatidylcholine, canbe used if needed to formulate the lipoic acid in a desired amount.

When folic acid, its salts or mixtures thereof is present, the amount offolic acid is preferably from about 0.001 g to about 10 g per dose(preferably in a 10 ml dose), including about 0.01 g, about 0.1 g, about1 g and about 5 g per dose. Preferably, the amount is from about 0.1 gto about 1.0 g per dose. More preferably, the amount is from about 0.2 gto about 0.5 g per dose. Solubility modifiers can be used if needed toformulate the lipoic acid in a desired amount.

One or more of an antibiotic, antiviral, antimicrobial or antisepticagent can be combined with MDSS to form a solution or the agent(s) canbe combined with a MDSS to form a composition. The agents contemplatedare those that are known in the art including, but not limited to,amoxicillin, levofloxacin, gatifloxacin, streptomycin, tetracycline,chloramphenicol, fluconazole, itraconazole and posaconazole. Effectiveamounts of these agents are also known. In particular, the MDSScompositions and solutions comprise erythromycin in about 500 mg perMDSS dose and/or about 30 mg of gentamicin per MDSS dose.

In a different embodiment, the present invention is directed to a methodof reducing the amount of a metal(s) in a subject in need thereof,increasing the excretion of a metal(s) or treating or ameliorating metalpoisoning. In one aspect, the metal is a heavy metal. In another aspect,the metal is selected from the group consisting of calcium, lead,uranium, plutonium, arsenic, molybdenum and mercury. In another aspect,the metal has an oxidation state of +1, +2 or +3. In another aspect, themetal is a transition or post-transition state metal. In another aspect,the metal is a divalent cation. Preferably, the metal is selected fromthe group consisting of Fe⁺³, HG⁺², Cu⁺², Ar⁺³, Pb₊₂, Co₊₂, Cd₊₂ andMn₊₂. In one aspect, the metal poisoning is acute. In a differentaspect, the metal poisoning is chronic. In a preferred embodiment, theMDSS solution for chelation comprises glycine. Glycine can complex withdivalent cations and enhance the metal sequestering and/or reducingeffect.

In another embodiment, the present invention is directed to a method ofincreasing the excretion of one or more toxins from a mammal, comprisingadministering to a subject by injection an effective amount of magneticdipole stabilized solution, wherein said excretion of one or more toxinsis increased. In this embodiment, the toxins are more soluble in theelectroactivated water and are eliminated from the body by excretion.

In yet another embodiment, the present invention is directed to a methodof providing nutrition support to a subject in need thereof, comprisingadministering to the subject an effective amount of magnetic dipolestabilized solution. The subject receiving nutritional support accordingto the invention may be a healthy subject, or a subject suffering from amalady selected from the group consisting of malnutrition, cachexia,diabetes, severe food allergies, short gut syndrome, cystic fibrosis,pancreatic disease, gastroenteritis, inflammatory bowel disease,intractable diarrhea, protein maldigestion, necrotizing enterocolitis,infectious diseases, hypermetabolism, trauma, eosinophilicgastroenteritis or gastroesophogeal reflux.

In another embodiment, the present invention is directed to a methodwherein the magnetic dipole stabilized solution comprises one or moretrace metals selected from the group consisting of Zn, Se, Cu, Mn andFe. In a preferred embodiment, the magnetic dipole stabilized solutionis an electroactivated water comprising from about 100 mg to about 500mg sodium ascorbate, from about 100 mg to about 500 mg magnesiumchloride 2H₂O, from about 100 mg to about 500 mg 2 di-methyl aminoethanol HCl, from about 1 mg to about 100 mg thiamine, from about 1 mgto about 100 mg riboflavine, from about 1 mg to about 300 mgnicotinamide, from about 1 mg to about 100 mg pyridoxine, from about 1mg to about 100 mg calcium pantothenate, from about 100 μg to about 500μg cyanobalamin, from about 1 mg to about 20 mg Zn, from about 1 mg toabout 100 mg Se, from about 1 mg to about 1000 mg Cu, Mn from about 0.01mg to about 10 mg, from about 1 mg to about 20 mg Fe andelectroactivated water. In a more preferred embodiment, the magneticdipole stabilized solution comprises about 395 mg sodium ascorbate,about 255 tug magnesium chloride 2H₂O, about 200 mg 2-di-methyl aminoethanol HCl, about 36 mg thiamine, about 7.3 mg riboflavine, about 100mg nicotinamide, about 18.2 mg pyridoxine, about 18.2 mg calciumpantothenate, about 320 μg cyanobalamin, about 10 mg Zn, about 45 mg Se,about 400 mg Cu, about 0.3 mg Mn, about 8 mg Fe, and electroactivatedwater.

In one aspect of the invention, the subject receiving nutritionalsupport has special dietary needs. The method comprises administering toa subject in need thereof by injection an effective amount of magneticdipole stabilized solution as described herein. Preferably, the specialdietary needs are associated with athletes, children, obese subjects,subjects undergoing chemotherapy for cancer, malnourished subjects orsubjects in a comatose state. In a preferred embodiment, the method ofthe invention is for aiding in weight loss. Weight gain is caused byconsuming more calories than the body requires for its basal metabolicfunctions and additional activities in which an individual is involved.The human body stores these excess calories as fatty deposits (lipids inadipose tissue) throughout the body, but is not able to readily accessthese fatty deposits to satisfy energy needs. To use these stored lipidsas an energy source, the number of calories ingested must be less thanthe total energy expenditure of the body (basal metabolic rate plusactivity level). Under hypocaloric conditions the body consumes fat as asource of fuel, but the switch to energy utilization of stored fat isnot instantaneous. The body has feedback mechanisms that attempt topreserve existing lipid stores. Therefore, in the interim between theinitial reduction in caloric intake and the conversion of lipids toenergy, the body consumes lean body mass as a source of energy. Hepaticgluconeogenesis utilizes amino acids from muscle to generate glucosewhich the body uses as its preferred energy source. Hence, the body willconsume some muscle tissue as its energy source during this period ofconversion. Reduced caloric intake usually induces cravings for foodthat reduce adherence to weight loss regimens. These cravings are causedby both psychological and physiological mechanisms. For example,ingested carbohydrates are absorbed from the digestive tract into thebloodstream to increase blood glucose levels. In response to theincrease in blood glucose, the pancreas releases insulin to aid in thetransport of glucose into the cells of the body where glucose isemployed as an energy source. However, if the amount of insulin releasedis greater than the amount of glucose present (which is often the casein overweight individuals), then the body reacts by signaling the brainto ingest more carbohydrates in order to balance the amount of insulinin the bloodstream. This insulin-induced craving for carbohydrates isvery common during periods of caloric restriction. The MDSS solutionsdescribed herein can treat or ameliorate the symptoms associated with areduced caloric intake.

In yet another embodiment, the present invention is directed to a methodof treating or ameliorating symptoms related to menopause. Menopause isa period after the cessation of normal ovulation cycles, during whichnormal menstruation ceases. A decrease in estradiol (E₂) productionaccompanies menopause, as the ovaries cease manufacture of E₂. Thisdecrease in E₂ production results in a shift in hormone balance in thebody, which often gives rise to a variety of symptoms associated withmenopause. Peri-menopause, which is also known as pre-menopause or theclimacteric, is a period prior to menopause during which normalovulation cycles gradually give way to cessation of menses. As theovulatory cycles lengthen and become more irregular, the level of E₂ mayinitially increase, but will eventually drop with the onset ofmenopause. Menopausal symptoms often accompany the drop in E₂ levels.The symptoms of peri-menopause, menopause and post-menopause includephysical symptoms such as hot flashes and sweating secondary tovasomotor instability. Additionally, psychological and emotionalsymptoms may accompany onset of climacteric, such as fatigue,irritability, insomnia, inability to concentrate, depression, memoryloss, headache, anxiety and nervousness. Additional symptoms can includeintermittent dizziness, paresthesias, palpitations and tachycardia aswell as nausea, constipation, diarrhea, arthralgia, myalgia, cold handsand feet and weight gain. In addition, changes to the genitals, urinaryincontinence, vaginal dryness, loss of pelvic muscle tone, increasedrisk of cardiovascular disease and osteoporosis increase with onset ofmenopause. Hot flashes are prevalent in, and bothersome to, manyperi-menopausal, menopausal and postmenopausal women. For decadeshormone replacement therapy with estrogens has been the standardtreatment for hot flashes, but many women have abandoned hormone therapy(HT) due to concerns about potential adverse effects, particularlybreast cancer. The MDSS compositions described herein are useful intreating or ameliorating one or more of the symptoms described above. Inan embodiment, the method comprises administering to a female subject inneed thereof by injection an effective amount of magnetic dipolestabilized solution as described herein.

In another embodiment, the present invention is directed to a kitcomprising a first vial containing a solution comprising one or moreselected from the group consisting of heparin, vitamins, salts, acids,lipoic acid, folic acid, antibiotic(s) and vitamers, and mixturesthereof; a second vial containing a magnetic dipole stabilized solution;and optionally instructions for use. Preferably, the first vial containsone or more selected from the group consisting of vitamins, salts, acidsand vitamers and mixtures thereof. Preferably in one aspect of thisembodiment, the magnetic dipole stabilized solution contained in the kitis electroactivated water. In another aspect, the first vial preferablycomprises lipoic acid and the amount of lipoic acid is preferably fromabout 10 mg to about 500 mg. Preferably, the amount of lipoic acid isfrom about 100 mg to about 400 mg. More preferably, the amount of lipoicacid is from about 250 mg to about 350 mg. Most preferably, the amountof lipoic acid is about 250 mg. Solubility modifiers can be used ifneeded to formulate the ingredients, including the lipoic acid, in adesired amount.

In a preferred embodiment, the kit contains a first vial comprisingsodium ascorbate, magnesium chloride 2H₂O, 2 di-methyl amino ethanolHCl, thiamine, riboflavine, nicotinamide, pyridoxine, calciumpantothenate and cyanobalamin. Optionally, the first vial can containfolic acid, lipoic acid and/or an antibiotic, such as erythromycin orgentamicin.

In another embodiment, the present subject matter is directed to a kitcomprising, a first vial containing a solution comprising, from about100 mg to about 500 mg sodium ascorbate, from about 100 mg to about 500mg magnesium chloride 2H₂O, from about 100 mg to about 500 mg 2di-methyl amino ethanol HCl, from about 1 mg to about 100 mg thiamine,from about 1 mg to about 100 mg riboflavine, from about 1 mg to about300 mg nicotinamide, from about 1 mg to about 100 mg pyridoxine, fromabout 1 mg to about 100 mg calcium pantothenate, from about 100 μg toabout 500 μg cyanobalamin, from about 1 mg to about 20 mg Zn, from about1 mg to about 100 mg Se, from about 1 mg to about 1000 mg Cu, from about0.01 mg to about 10 mg Mn and from about 1 mg to about 20 mg Fe, and asecond vial containing a magnetic dipole stabilized solution; andoptionally instructions for use. In a preferred embodiment, the magneticdipole stabilized solution is electroactivated water. Preferably, themagnetic dipole stabilized solution comprises electroactivated water.

Electroactivated water can be prepared using methods, apparatus, andsystems disclosed in, for example, Van Kalken et al., InternationalPatent Application No. PCT/US2011/020691, Davis et al. U.S. Pat. No.7,374,645, and/or Daly et al. U.S. Pat. No. 7,691,249, which areincorporated herein by reference. The ORP of the electroactivated wateris that of the neutral anolyte, which has a positive ORP, preferablyabove +100 mV. Also preferred are values of above +200 mV, above +300mV, +400 mV, above +500 mV, +600 mV, above +700 mV, +800 mV, above +900mV and +1000 mV. The magnetic dipole stabilized solution for injectionhowever preferably has a negative or neutral electric potential onceadditional components, e.g., vitamins are combined to the contents ofvials in a kit are combined. In a preferred embodiment of this aspect,the negative potential is below about −990 mV. In a preferredembodiment, the potential is from about −990 mV to about −0.0001 mV.More preferably, the potential is from about −150 mV to about −5 mV.Also more preferred is a potential from about −120 mV to about −20 mV.Most preferably, the potential is about −70 mV.

In one embodiment, the MDSS composition comprises2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide or derivativesthereof. Not to be bound by theory, the MDSS can hydrolyze the activeingredient in situ thereby enhancing its effect on channel blocking,cyclooxigenase activity and enzyme induction. More particularly, when2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide is present in the MDSSsolution, it can be hydrolysed in situ to form the analogues of formula(I):

wherein, R₁ is an alkyl, carboxamide or aminocarbamyl moiety; and R₂ isa methyl, ethyl, methoxy or carbonyl moiety. The pharmaceuticalcomposition may include between 2.5% and 3.5% of the active ingredientand may have a pH of about 2.5 to about 3.5.

In an embodiment, a method is provided for activating a pharmaceuticalcomposition in situ, the pharmaceutical composition including an activeingredient selected from the group consisting of2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide and its analogues,pharmaceutically acceptable salts, metabolites and esters thereof; and acarrier in the form of a magnetic dipole stabilized solution havinganti-microbial properties; wherein a source of carbon dioxide isprovided in the pharmaceutical composition prior to administrationthereof. The source of carbon dioxide may be sodium bicarbonate. It isenvisaged that the introduction of a source of carbon dioxide shallenhance the activity of the ionized portion of the active ingredient soas to thereby increase the efficacy of the pharmaceutical composition.

The magnetic dipole stabilized solution can further comprise othercomponents. Specifically, the magnetic dipole stabilized solution, whichpreferably comprises electroactivated water, further comprises one ormore independently selected from the group consisting of vitamins,salts, acids, amino acids or salts thereof, vitamers, di-methyl aminoethanol, anesthetic(s), stabilized oxidative species, heparin and lipoicacid, and mixtures thereof. Thus, in some embodiments, thepharmaceutical composition may further include nutrients suitable ascofactors for enzymes, vitamins suitable for rapid cellular energyproduction, pH modifiers and buffer components. The nutrients may beselected from the group consisting of amino acids, carbohydrates andlipids, and a combination thereof. In some embodiments, the combinationof nutrients with MDSS can result in a synergistically enhanced effectof the active ingredient. More particularly, the nutrients are electroactivated by the MDSS and improved delivery across the cell membranethereof.

Carbohydrates, such as simple or complex sugars or cyclicoligosaccharides, can be a component of a MDSS composition. Preferably,the carbohydrate is fructose or a cyclodextrin, such a betacyclodextrinor hydroxypropyl cyclodextrin. When present, the cyclodextrin is in anamount of from about 0.001 to about 10 mg. Preferably, the amount isfrom about 0.05 to about 1.0 mg. Most preferably, the amount is fromabout 0.01 to about 0.5 mg.

Other compounds and molecules that can be a component of a MDSS solutionare molecules, which also referred to as minerals. Those that are neededby the body in relatively large amounts are sodium, potassium, chlorine,calcium, phosphorus and magnesium. Those that are needed in smalleramounts are “trace” minerals and include selenium, iron, zinc,manganese, molybdenum, chromium, fluoride, iodine, copper and the like.

Another component of a MDSS composition can be one or more amino acidsor salts or esters thereof. Preferably, the amino acid(s) is selectedfrom the group consisting of glycine, alanine, arginine, glutamic acidand tyrosine and salts or esters thereof.

A preferred component is lipoic acid. Lipoic acid can be a racemicmixture or can be separated into its R and S enantiomers. The Renantiomer form of lipoic acid is preferred because it is the naturalform. It has the structure:

Buffer components selected from the group consisting of phosphoric acidand its salts or acetic acid and its salts, and pH modifiers selectedfrom the group consisting of succinic acid, sulphuric acid, hydrochloricacid, sodium hydroxide, sodium bicarbonate and ethanolamine compounds,may also be included in the composition.

Oxidative species which can be in the composition are selected from thegroup consisting of H₂O, O₂, H₂O₂, Cl₂O, H₃O, O₃ and ClO₃.

An effective amount is the amount required to provide the subject withan improvement in a symptom or underlying condition. Many conditions canhave subjective markers to gauge improvement, such as in the case ofalopecia and acne. Therefore an effective amount is an amount thatprovides an improvement as gauged by the subject or by the provider.Some conditions have clinical markers. In these cases, an effectiveamount is an amount that provides an improvement by way of markersdetermined by clinical assessment. This, of course, is only one way ofgauging an improvement in the symptom or condition to be treated.Finally, some conditions can have improvement based on subjective and/orclinical markers. The MDSS compositions will generally be used in anamount effective to achieve the intended result, for example in anamount effective to treat, prevent the particular condition in the firstplace or ameliorate the symptoms. MDSS compositions can be administeredtherapeutically to achieve therapeutic benefit or prophylactically toachieve prophylactic benefit. By therapeutic benefit is meanteradication or amelioration of the underlying disorder being treatedand/or eradication or amelioration of one or more of the symptomsassociated with the underlying disorder such that the patient reports animprovement in feeling or condition, notwithstanding that the patientcan still be afflicted with the underlying disorder. For example,administration of a MDSS composition to a patient suffering from a skincondition provides therapeutic benefit not only when the underlying skincondition is eradicated or ameliorated, but also when the patientreports a decrease in the severity or duration of the symptomsassociated with the skin condition. Therapeutic benefit also includeshalting or slowing the progression of the disease, regardless of whetherimprovement is realized.

A therapeutically effective amount of the compositions of the presentinvention will generally mean administration of from about 0.001 ml/kgto about 1.0 ml/kg (weight of active solution/body weight of mammal).Preferably the amount is from about 0.01 ml/kg to about 1.0 ml/kg.However, an effective amount may vary from mammal to mammal and caneasily be adjusted by one of ordinary skill by varying the volume andfrequency of administrations. The amount of composition administeredwill depend upon a variety of factors, including, for example, theparticular indication being treated, the mode of administration, whetherthe desired benefit is prophylactic or therapeutic, the severity of theindication being treated and the age and weight of the patient, thebioavailability of the particular composition, and the like.Determination of an effective dosage is well within the capabilities ofthose skilled in the art coupled with the general and specific examplesdisclosed herein. When used prophylactically, the same principles andguidelines of dosing apply. The administration can occur in oneinfusion, but more preferably is delivered over one to five infusionsper week, lasting for several weeks or months.

Practice of the method of the present invention comprises administeringto a subject a therapeutically effective amount of a MDSS composition inany suitable systemic or local formulation, in an amount effective todeliver a dosage. In practicing the method of treatment or use of thepresent methods, a therapeutically effective amount of a MDSScomposition is administered to a mammal either alone or in combinationwith other therapies. A preferred combination in all embodimentsincludes a method of administering a magnetic dipole stabilized solutioncombined with a separate vitamin regimen. As used herein, the term“regimen” means a deliberate administration or consumption of one ormore vitamin(s) either as a single dose or as daily or weekly dosages.In these embodiments, the vitamins can be administered or consumed inany fashion to provide a mammal with the desired amount of vitamin(s).In these embodiments, the MDSS composition itself may or may not includevitamins. In other words, it is contemplated that the methods includeadministration of an MDSS composition in combination with vitamins,wherein the vitamins are administered or consumed in a separatecomposition either contemporaneous with the administration of an MDSScomposition or at a different time. The period of time between the MDSSadministration and the vitamin(s) administration or consumption can be aday, a week or more. The MDSS therapies described herein are preferablyprovided in administrations over weeks. Thus, any vitamin regimen withinthat time is contemplated in the methods described herein. Morepreferred time periods are MDSS administration within about one week ofvitamin(s) administration or consumption. More preferably, an MDSSadministration is within about one day of the vitamin(s) administrationor consumption. Preferably, the vitamin regimen comprises a vitaminsupplement or multivitamin consumed orally as a one-time dose or dailyor weekly doses. Particularly preferred are vitamin regimens thatprovide a multivitamin or a composition comprising one or more of thevitamins disclosed herein in the disclosed amounts. More specifically,the vitamins are selected from families of vitamins selected from thegroup consisting of A (2000 to 25000 IU/dose), B1 (10 to 100 mg/dose),B2 (1 to 400 mg/dose), B3 (10 to 200 mg/dose), B5 (25 to 100 mg/dose),B6 (1 to 200 mg/dose), B12 (0.4 to 1500 μg/dose), C (10 to 2000mg/dose), D (200 to 800 IU/dose), E (6 to 800 IU/dose) and K (70 to 500μg/dose) and vitamers thereof. Also contemplated are combinationtherapies that include other supplements such as an antioxidant,beta-carotene, chromium picolinate, co-enzyme Q-10, conjugated linoleicacid, fish oil, iodine, L-arginine, Lecithin, L-lysine, Lutein, tracemetals, soy isoflavones, glucosamine, chondroitin, melatonin, St. John'swort, pantothenic acid and S-adenosylmethionine. Again, just asdescribed above for vitamin(s), these supplements are administered incombination with MDSS but not necessarily at the same time or in thesame composition.

Routes of administration for a therapeutically effective amount of anMDSS composition include, but are not limited to, intravenous orparenteral administration, oral administration, topical administration,transmucosal administration and transdermal administration. Forintravenous or parenteral administration, i.e., injection or infusion,the MDSS composition may also contain suitable pharmaceutical diluentsand carriers, such as water, saline, dextrose solutions, fructosesolutions, ethanol, or oils of animal, vegetative, or synthetic origin.It may also contain preservatives, and buffers as are known in the art.When a therapeutically effective amount is administered by intravenous,cutaneous or subcutaneous injection, the solution can also containcomponents to adjust pH, isotonicity, stability, and the like, all ofwhich is within the skill in the art. A MDSS composition forintravenous, cutaneous, or subcutaneous injection should contain, inaddition to peptide an isotonic vehicle such as Sodium ChlorideInjection, Ringer's Injection, Dextrose Injection, Dextrose and SodiumChloride Injection, Lactated Ringer's Injection Citrate Buffer pH 5.5,or other carriers, diluents and additives as known in the art. Asdescribed fully elsewhere herein, the pharmaceutical composition of thepresent invention may also contain stabilizers, preservatives, buffers,antioxidants, or other additive known to those of skill in the art. Thepharmaceutical compositions are formulated for intravenous or parenteraladministration. Typically, compositions for intravenous or parenteraladministration comprise a suitable sterile solvent, which may be anisotonic aqueous buffer or pharmaceutically acceptable organic solvent.As described fully elsewhere herein, where necessary, the compositionscan also include a solubilizing agent. Compositions for intravenous orparenteral administration can optionally include a local anesthetic tolessen pain at the site of the injection. Generally, the ingredients aresupplied either separately or mixed together in unit dosage form in ahermetically sealed container such as an ampoule or sachette. Thepharmaceutical compositions for administration by injection or infusioncan be dispensed, for example, with an infusion bottle containing, forexample, sterile pharmaceutical grade water or saline. Where thepharmaceutical compositions are administered by injection, an ampoule ofsterile water for injection, saline, or other solvent such as apharmaceutically acceptable organic solvent can be provided so that theingredients can be mixed prior to administration.

The duration of intravenous therapy using the pharmaceutical compositionof the present invention will vary, depending on the condition beingtreated or ameliorated and the condition and potential idiosyncraticresponse of each individual mammal. The duration of each infusion isfrom about 1 minute to about 1 hour. The infusion can be repeated within24 hours. Thus, a mammal can receive about 1 to about 5 infusions perday. Preferably, the number of infusions per day is 1 or 2. The periodbetween each infusion can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hoursor more. Alternatively, the infusions can be given one after anotherwithout a substantial period in between. In one embodiment, the infusionlasts about 45 minutes. The dose may be repeated 2-3 times a weekdepending on the severity of the relative or absolute deficits ofnutrients in the patient. A clinical assessment may be necessary inorder to establish the status, but can be limited to a review of medicalhistory, subjective review of symptoms, the subjective opinion of themammal when human or review of any specific deficits.

Systemic formulations include those designed for administration byinjection, e.g., subcutaneous, intravenous, intramuscular, intrathecalor intraperitoneal injection. Useful injectable preparations includesterile suspensions, solutions or emulsions of the active compound(s) inaqueous or oily vehicles. The compositions also can contain solubilizingagents, formulating agents, such as suspending, stabilizing and/ordispersing agent. The formulations for injection can be presented inunit dosage form, e.g., in ampules or in multi-dose containers, and cancontain added preservatives. For prophylactic administration, thecompound can be administered to a patient at risk of developing one ofthe previously described conditions or diseases. Alternatively,prophylactic administration can be applied to avoid the onset ofsymptoms in a patient suffering from or formally diagnosed with theunderlying condition.

The amount of compound administered will depend upon a variety offactors, including, for example, the particular indication beingtreated, the mode of administration, whether the desired benefit isprophylactic or therapeutic, the severity of the indication beingtreated and the age and weight of the patient, the bioavailability ofthe particular active compound, and the like. Determination of aneffective dosage is well within the capabilities of those skilled in theart coupled with the general and specific examples disclosed herein.

Oral administration of an MDSS composition can be accomplished usingdosage forms including, but not limited to, capsules, caplets,solutions, suspensions and/or syrups. Such dosage forms are preparedusing conventional methods known to those in the field of pharmaceuticalformulation and described in the pertinent texts, e.g., in Remington:The Science and Practice of Pharmacy (2000), supra.

The dosage form may be a capsule, in which case the activeagent-containing composition may be encapsulated in the form of aliquid. Suitable capsules may be either hard or soft, and are generallymade of gelatin, starch, or a cellulosic material, with gelatin capsulespreferred. Two-piece hard gelatin capsules are preferably sealed, suchas with gelatin bands or the like. See, for e.g., Remington: The Scienceand Practice of Pharmacy (2000), supra, which describes materials andmethods for preparing encapsulated pharmaceuticals.

Capsules may, if desired, be coated so as to provide for delayedrelease. Dosage forms with delayed release coatings may be manufacturedusing standard coating procedures and equipment. Such procedures areknown to those skilled in the art and described in the pertinent texts(see, for e.g., Remington: The Science and Practice of Pharmacy (2000),supra). Generally, after preparation of the capsule, a delayed releasecoating composition is applied using a coating pan, an airless spraytechnique, fluidized bed coating equipment, or the like. Delayed releasecoating compositions comprise a polymeric material, e.g., cellulosebutyrate phthalate, cellulose hydrogen phthalate, cellulose proprionatephthalate, polyvinyl acetate phthalate, cellulose acetate phthalate,cellulose acetate trimellitate, hydroxypropyl methylcellulose phthalate,hydroxypropyl methylcellulose acetate, dioxypropyl methylcellulosesuccinate, carboxymethyl ethylcellulose, hydroxypropyl methylcelluloseacetate succinate, polymers and copolymers formed from acrylic acid,methacrylic acid, and/or esters thereof.

Sustained-release dosage forms provide for drug release over an extendedtime period, and may or may not be delayed release. Generally, as willbe appreciated by those of ordinary skill in the art, sustained-releasedosage forms are formulated by dispersing a drug within a matrix of agradually bioerodible (hydrolyzable) material such as an insolubleplastic, a hydrophilic polymer, or a fatty compound. Insoluble plasticmatrices may be comprised of, for example, polyvinyl chloride orpolyethylene. Hydrophilic polymers useful for providing a sustainedrelease coating or matrix cellulosic polymers include, withoutlimitation: cellulosic polymers such as hydroxypropyl cellulose,hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methylcellulose, ethyl cellulose, cellulose acetate, cellulose acetatephthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulosephthalate, hydroxypropylcellulose phthalate, cellulosehexahydrophthalate, cellulose acetate hexahydrophthalate, andcarboxymethylcellulose sodium; acrylic acid polymers and copolymers,preferably formed from acrylic acid, methacrylic acid, acrylic acidalkyl esters, methacrylic acid alkyl esters, and the like, e.g.copolymers of acrylic acid, methacrylic acid, methyl acrylate, ethylacrylate, methyl methacrylate and/or ethyl methacrylate, with aterpolymer of ethyl acrylate, methyl methacrylate andtrimethylammonioethyl methacrylate chloride (sold under the tradenameEudragit RS) preferred; vinyl polymers and copolymers such as polyvinylpyrrolidone, polyvinyl acetate, polyvinylacetate phthalate, vinylacetatecrotonic acid copolymer, and ethylene-vinyl acetate copolymers; zein;and shellac, ammoniated shellac, shellac-acetyl alcohol, and shellacn-butyl stearate. Fatty compounds for use as a sustained release matrixmaterial include, but are not limited to, waxes generally (e.g.,carnauba wax) and glyceryl tristearate.

Topical administration of an MDSS composition can be accomplished usingany formulation suitable for application to the body surface, and maycomprise, for example, an ointment, cream, gel, lotion, solution, pasteor the like, and/or may be prepared so as to contain liposomes,micelles, and/or microspheres. Preferred topical formulations herein areointments, creams, and gels.

Ointments, as is well known in the art of pharmaceutical formulation,are semisolid preparations that are typically based on petrolatum orother petroleum derivatives. The specific ointment base to be used, aswill be appreciated by those skilled in the art, is one that willprovide for optimum drug delivery, and, preferably, will provide forother desired characteristics as well, e.g., emolliency or the like. Aswith other carriers or vehicles, an ointment base should be inert,stable, nonirritating and nonsensitizing. As explained in Remington: TheScience and Practice of Pharmacy (2000), supra, ointment bases may begrouped in four classes: oleaginous bases; emulsifiable bases; emulsionbases; and water-soluble bases. Oleaginous ointment bases include, forexample, vegetable oils, fats obtained from animals, and semisolidhydrocarbons obtained from petroleum. Emulsifiable ointment bases, alsoknown as absorbent ointment bases, contain little or no water andinclude, for example, hydroxystearin sulfate, anhydrous lanolin andhydrophilic petrolatum. Emulsion ointment bases are either water-in-oil(W/O) emulsions or oil-in-water (O/W) emulsions, and include, forexample, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid.Preferred water-soluble ointment bases are prepared from polyethyleneglycols of varying molecular weight (See, e.g., Remington: The Scienceand Practice of Pharmacy (2002), supra).

Creams, as also well known in the art, are viscous liquids or semisolidemulsions, either oil-in-water or water-in-oil. Cream bases arewater-washable, and contain an oil phase, an emulsifier and an aqueousphase. The oil phase, also called the “internal” phase, is generallycomprised of petrolatum and a fatty alcohol such as cetyl or stearylalcohol. The aqueous phase usually, although not necessarily, exceedsthe oil phase in volume, and generally contains a humectant. Theemulsifier in a cream formulation is generally a nonionic, anionic,cationic or amphoteric surfactant.

As will be appreciated by those working in the field of pharmaceuticalformulation, gels-are semisolid, suspension-type systems. Single-phasegels contain organic macromolecules distributed substantially uniformlythroughout the carrier liquid, which is typically aqueous, but also,preferably, contain an alcohol and, optionally, an oil. Preferred“organic macromolecules,” i.e., gelling agents, are crosslinked acrylicacid polymers such as the “carbomer” family of polymers, e.g.,carboxypolyalkylenes that may be obtained commercially under theCarbopol® trademark. Also preferred are hydrophilic polymers such aspolyethylene oxides, polyoxyethylene-polyoxypropylene copolymers andpolyvinylalcohol; cellulosic polymers such as hydroxypropyl cellulose,hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropylmethylcellulose phthalate, and methylcellulose; gums such as tragacanthand xanthan gum; sodium alginate; and gelatin. In order to prepare auniform gel, dispersing agents such as alcohol or glycerin can be added,or the gelling agent can be dispersed by trituration, mechanical mixing,and/or stirring.

Various additives, known to those skilled in the art, may be included inthe topical formulations. For example, solubilizers may be used tosolubilize certain active agents. For those drugs having an unusuallylow rate of permeation through the skin or mucosal tissue, it may bedesirable to include a permeation enhancer in the formulation; suitableenhancers are as described elsewhere herein.

Transmucosal administration of an MDSS composition can be accomplishedusing any type of formulation or dosage unit suitable for application tomucosal tissue. For example, an MDSS composition may be administered tothe buccal mucosa in an adhesive patch, sublingually or lingually as acream, ointment, or paste, nasally as droplets or a nasal spray, or byinhalation of an aerosol formulation or a non-aerosol liquidformulation.

Preferred buccal dosage forms will typically comprise a therapeuticallyeffective amount of an MDSS composition and a bioerodible (hydrolyzable)polymeric carrier that may also serve to adhere the dosage form to thebuccal mucosa. The buccal dosage unit is fabricated so as to erode overa predetermined time period, wherein drug delivery is providedessentially throughout. The time period is typically in the range offrom about 1 hour to about 72 hours. Preferred buccal deliverypreferably occurs over a time period of from about 2 hours to about 24hours. Buccal drug delivery for short-term use should preferably occurover a time period of from about 2 hours to about 8 hours, morepreferably over a time period of from about 3 hours to about 4 hours. Asneeded buccal drug delivery preferably will occur over a time period offrom about 1 hour to about 12 hours, more preferably from about 2 hoursto about 8 hours, most preferably from about 3 hours to about 6 hours.Sustained buccal drug delivery will preferably occur over a time periodof from about 6 hours to about 72 hours, more preferably from about 12hours to about 48 hours, most preferably from about 24 hours to about 48hours. Buccal drug delivery, as will be appreciated by those skilled inthe art, avoids the disadvantages encountered with oral drugadministration, e.g., slow absorption, degradation of the active agentby fluids present in the gastrointestinal tract and/or first-passinactivation in the liver.

The “therapeutically effective amount” of an MDSS composition in thebuccal dosage unit will of course depend on the potency of an MDSScomposition and the intended dosage, which, in turn, is dependent on theparticular individual undergoing treatment, the specific indication, andthe like. The buccal dosage unit will generally contain from about 1.0wt. % to about 60 wt. % active agent, preferably on the order of fromabout 1 wt. % to about 30 wt. % active agent. With regard to thebioerodible (hydrolyzable) polymeric carrier, it will be appreciatedthat virtually any such carrier can be used, so long as the desired drugrelease profile is not compromised, and the carrier is compatible withan MDSS composition and any other components of the buccal dosage unit.Generally, the polymeric carrier comprises a hydrophilic (water-solubleand water-swellable) polymer that adheres to the wet surface of thebuccal mucosa. Examples of polymeric carriers useful herein includeacrylic acid polymers and co, e.g., those known as “carbomers”(Carbopol®, which may be obtained from B. F. Goodrich, is one suchpolymer). Other suitable polymers include, but are not limited to:hydrolyzed polyvinylalcohol; polyethylene oxides (e.g., Sentry Polyox®water soluble resins, available from Union Carbide); polyacrylates(e.g., Gantrez®, which may be obtained from GAF); vinyl polymers andcopolymers; polyvinylpyrrolidone; dextran; guar gum; pectins; starches;and cellulosic polymers such as hydroxypropyl methylcellulose, (e.g.,Methocel®, which may be obtained from the Dow Chemical Company),hydroxypropyl cellulose (e.g., Klucel®, which may also be obtained fromDow), hydroxypropyl cellulose ethers (see, e.g., U.S. Pat. No. 4,704,285to Alderman), hydroxyethyl cellulose, carboxymethyl cellulose, sodiumcarboxymethyl cellulose, methyl cellulose, ethyl cellulose, celluloseacetate phthalate, cellulose acetate butyrate, and the like.

Other components may also be incorporated into the buccal dosage formsdescribed herein. The additional components include, but are not limitedto, disintegrants, diluents, binders, lubricants, flavoring, colorants,preservatives, and the like. Examples of disintegrants that may be usedinclude, but are not limited to, cross-linked polyvinylpyrrolidones,such as crospovidone (e.g., Polyplasdone® XL, which may be obtained fromGAF), cross-linked carboxylic methylcelluloses, such as croscarmelose(e.g., Ac-di-sol®, which may be obtained from FMC), alginic acid, andsodium carboxymethyl starches (e.g., Explotab®, which may be obtainedfrom Edward Medell Co., Inc.), methylcellulose, agar bentonite andalginic acid. Suitable diluents are those which are generally useful inpharmaceutical formulations prepared using compression techniques, e.g.,dicalcium phosphate dihydrate (e.g., Di-Tab®, which may be obtained fromStauffer), sugars that have been processed by cocrystallization withdextrin (e.g., co-crystallized sucrose and dextrin such as Di-Pak®,which may be obtained from Amstar), calcium phosphate, cellulose,kaolin, mannitol, sodium chloride, dry starch, powdered sugar and thelike. Binders, if used, are those that enhance adhesion. Examples ofsuch binders include, but are not limited to, starch, gelatin and sugarssuch as sucrose, dextrose, molasses, and lactose. Particularly preferredlubricants are stearates and stearic acid, and an optimal lubricant ismagnesium stearate.

Sublingual and lingual dosage forms include creams, ointments andpastes. The cream, ointment or paste for sublingual or lingual deliverycomprises a therapeutically effective amount of the selected activeagent and one or more conventional nontoxic carriers suitable forsublingual or lingual drug administration. The sublingual and lingualdosage forms of the present invention can be manufactured usingconventional processes. The sublingual and lingual dosage units arefabricated to disintegrate rapidly. The time period for completedisintegration of the dosage unit is typically in the range of fromabout 10 seconds to about 30 minutes, and optimally is less than 5minutes.

Other components may also be incorporated into the sublingual andlingual dosage forms described herein. The additional componentsinclude, but are not limited to binders, disintegrants, wetting agents,lubricants, and the like. Examples of binders that may be used includewater, ethanol, polyvinylpyrrolidone; starch solution gelatin solution,and the like. Suitable disintegrants include dry starch, calciumcarbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, lactose, and the like. Wetting agents,if used, include glycerin, starches, and the like. Particularlypreferred lubricants are stearates and polyethylene glycol. Additionalcomponents that may be incorporated into sublingual and lingual dosageforms are known, or will be apparent, to those skilled in this art (See,e.g., Remington: The Science and Practice of Pharmacy (2000), supra).

Other preferred compositions for sublingual administration include, forexample, a bioadhesive to retain an MDSS composition sublingually; aspray, paint, or swab applied to the tongue; or the like. Increasedresidence time increases the likelihood that the administered inventioncan be absorbed by the mucosal tissue.

Transdermal administration of MDSS compositions through the skin ormucosal tissue can be accomplished using conventional transdermal drugdelivery systems, wherein the agent is contained within a laminatedstructure (typically referred to as a transdermal “patch”) that servesas a drug delivery device to be affixed to the skin.

Transdermal drug delivery may involve passive diffusion or it may befacilitated using electrotransport, e.g., iontophoresis. In a typicaltransdermal “patch,” the drug composition is contained in a layer, or“reservoir,” underlying an upper backing layer. The laminated structuremay contain a single reservoir, or it may contain multiple reservoirs.In one type of patch, referred to as a “monolithic” system, thereservoir is comprised of a polymeric matrix of a pharmaceuticallyacceptable contact adhesive material that serves to affix the system tothe skin during drug delivery. Examples of suitable skin contactadhesive materials include, but are not limited to, polyethylenes,polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and thelike.

Alternatively, the drug-containing reservoir and skin contact adhesiveare separate and distinct layers, with the adhesive underlying thereservoir which, in this case, may be either a polymeric matrix asdescribed above, or it may be a liquid or hydrogel reservoir, or maytake some other form.

The backing layer in these laminates, which serves as the upper surfaceof the device, functions as the primary structural element of thelaminated structure and provides the device with much of itsflexibility. The material selected for the backing material should beselected so that it is substantially impermeable to the active agent andany other materials that are present, the backing is preferably made ofa sheet or film of a flexible elastomeric material. Examples of polymersthat are suitable for the backing layer include polyethylene,polypropylene, polyesters, and the like.

During storage and prior to use, the laminated structure includes arelease liner. Immediately prior to use, this layer is removed from thedevice to expose the basal surface thereof, either the drug reservoir ora separate contact adhesive layer, so that the system may be affixed tothe skin. The release liner should be made from a drug/vehicleimpermeable material.

Transdermal drug delivery systems may in addition contain a skinpermeation enhancer. That is, because the inherent permeability of theskin to some drugs may be too low to allow therapeutic levels of thedrug to pass through a reasonably sized area of unbroken skin, it isnecessary to co-administer a skin permeation enhancer with such drugs.Suitable enhancers are well known in the art and include, for example,those enhancers listed below in transmucosal compositions.

As stated above, the MDSS compositions described herein may includevitamins and vitamers, which is a substance(s) that has vitamin-likeactivity. Vitamins selected from the group consisting of the watersoluble and lipid soluble group, and a combination of two or morethereof may also be added to the pharmaceutical composition. Preferablythe pharmaceutical composition includes ascorbic acid. It is envisagedthat the ascorbic acid will increase the negative and stabilize theanti-oxidant properties of the formulation. Ascorbic acid is included asa strong anti-oxidant component and to maintain the structural integrityof connective tissue, including epithelial basement membranes and topromote wound healing. It may also play a distinct role as an agent withstrong anti-inflammatory actions. The oxidized form of the vitamin hasbeen shown to transfer intracellularly where some of it is reducedwithin the cell. Deficiencies of other B group and A and E are alsoprotected by this vitamin. The B Group of Vitamins has been shown to beimportant in human food intake, and plays an important role acting asco-enzymes in cellular metabolism and energy production. The entire Bgroup of vitamins is included in the formulation in order to ensure thatall vitamins are present so that any deficiencies may addressed in thepatient population to be treated with this product. The B group vitaminsare always found together to occur naturally together in foods and areincluded for this reason. The B group includes: 1) Thiamine (B1), whichplays an important role in energy production within the cell,specifically as co-enzyme in metabolism of carbohydrates. At least 24enzymes are known to use thiamine as a co-enzyme; 2) Riboflavin (B2) inthe form of flavin mononucleotide and flavin adenine dinucleotide arepart of all dehydrogenase enzymes. Deficiency of this vitamin causesinflammation of the mouth, tongue, dermatitis, defective vision andblood dyscrasias; 3) Niacinamide (B3) is included, as part of the Bgroup of vitamins as deficiency syndromes in clinical pellagra are wellknown clinical manifestations of deficiencies. The deficiency states ofthis vitamin are associated with intestinal diseases and alcohol misuse.It also occurs in diabetes mellitus and carcinoid syndrome. The activeforms of this vitamin include the nicotinamide dinucleotides NAD andNADP, which are the co-enzymes and co-substrates for numerousdehydrogenases responsible for oxidation-reduction systems within thehuman cell, which are indispensable for energy production. The formationof nicotinic acid from the administered nicotinamide in the formulationproduce nicotinic acid possessing additional actions not shared bynicotinamide, such as inhibition of cholesterol synthesis; 4) CalciumD-Pantothenate (B5), pantothenic acid forms a major part of the moleculeof co-enzyme A, which is important in the energy producing metaboliccycles in the mitochondria of all cells. The effect of this vitamin onvarious disease syndromes has been recognized. Such as its use inneurotoxicity produced by streptomycin and its use in diabeticneuropathy, skin diseases and adynamic ileus; and 5) Pyridoxine (B6) iswidely utilized as a co-enzyme in over 40 types of enzymatic reactions.The most important of these are the transamination reactions and theinfluence of pyridoxine on tryptophane metabolism. Kynureminase which isa the enzyme used to identify pyridoxine deficiencies, loses itsactivity when pyridoxine is not present and may result in secondarynicotinic acid deficiency as a result of lack of the kynureminaseconversion of nicotinic acid from tryptophane.

Cyanocobalamin (B12) is used because of the frequent reports ofmal-absorption of cyanocobalamin, caused by poor dietary habitssenescence and certain drugs (metformin) used as a hypoglycemic agent indiabetes mellitus. This vitamin is essential for normal erythropoeisisto occur and recent findings have also implicated this vitamin withimprovement of neuronal transmission in motor neuron disease.

Vitamin K is a fat soluble vitamin. There are two naturally occurringforms of the vitamin. Vitamin K1 is the dietary Vitamin K and isabundant in green leafy vegetables, whereas vitamin K2 is present intissues. Vitamin K2 is synthesized by bacteria. It is found mainly infermented products like fermented soybeans, cheese, curds and to someextent also in meat and meat products (Thijssen, H. H., M. J.Drittij-Reijnders, and M. A. Fischer, 1996, Phylloquinone andmenaquinone-4 distribution in rats: synthesis rather than uptakedetermines menaquinone-4 organ concentrations, J Nutr 126:537-43).Vitamin K2 is found in animals as menaquinone. It is the human activatedform of vitamin K and is said to promote the healing of bone fractures.It is essential for the carboxylation of glutamate residues in manycalcium binding proteins such as calbindin and osteocalcin. Theseproteins are involved in calcium uptake and bone mineralization. Thereis no established daily dosage for vitamin K2 but only for Vitamin K1. Atypical therapeutic oral dose for vitamin K2 for osteoporosis is 45mg/day. Therapeutic dose for cancer patients is 25 mg/day, but usuallyis in the range of 45 mg/day. Unlike for coagulation, we need muchhigher levels of vitamin K for complete gamma-carboxylation ofosteocalcin. Vitamin K deficiency is associated with reduced hip bonemineral density and increased fracture risk in healthy elderly women.Animal studies have shown that the most potent form of vitamin K isvitamin K2, which was administered to rats at 0.1 mg/kg orally. VitaminK2, in the form of menaquinone-4, is the most biologically active form.Vitamin K2 is a cofactor of gamma-carboxilase and thus essential for thecarboxylation of glutamate residues in many calcium binding proteinssuch as calbindin and osteocalcin (Shearer, M. J., 1992, Vitamin Kmetabolism and nutriture, Blood Rev 6:92-104). These proteins areinvolved in calcium uptake and bone mineralization, hence vitamin K2 issaid to promote the healing of bone fractures (Hara, K., Y. Akiyama, T.Nakamura, S. Murota, and I. Morita, 1995, The inhibitory effect ofvitamin K2 (menatetrenone) on bone resorption may be related to its sidechain, Bone 16:179-84).

Unlike for coagulation, a much higher level of vitamin K is needed forcomplete gamma-carboxylation of osteocalcin (Booth, S. L., and J. W.Suttie, 1998, Dietary intake and adequacy of vitamin K, J. Nutr128:785-8). Vitamin K deficiency is associated with reduced hip bonemineral density and increased fracture risk in healthy elderly women.Animal studies have shown that the most potent form of vitamin K isvitamin K2, which was administered to rats at 0.1 mg/kg orally (Akiyama,Y., K. Hara, A. Matsumoto, S. Takahashi, and T. Tajima, 1995, Comparisonof intestinal absorption of vitamin K2 (menaquinone) homologues andtheir effects on blood coagulation in rats with hypoprothrombinaemia,Biochem Pharmacol 49:1801-7). Vitamin K2, in the form of menaquinone-4,is the most biologically active form. It has been extensively studied inthe treatment of osteoporosis. In one of these studies, 241 osteoporoticwomen were given 45 mg/day vitamin K2 and 150 mg elemental calcium.After two years, vitamin K2 was shown to maintain lumbar bone mineraldensity, significant lower fracture incidence (10% versus 30% in thecontrol group (Shiraki, M., Y. Shiraki, C. Aoki, and M. Miura, 2000,Vitamin K2 (menatetrenone) effectively prevents fractures and sustainslumbar bone mineral density in osteoporosis, J Bone Miner Res15:515-21).

Vitamin K2, but not K1, may inhibit the calcification of arterialplaque. In 1996, animal studies involving rats found high dose ofVitamin K2 (100 mg/kg body weight daily) inhibited the increase incalcium in both kidneys and aorta induced by megadose of syntheticvitamin D (Seyama, Y., M. Horiuch, M. Hayashi, and Y. Kanke, 1996,Effect of vitamin K2 on experimental calcinosis induced by vitamin D2 inrat soft tissue, Int J Vitam Nutr Res 66:36-8). A similar study wasconducted with rabbits. High dose of Vitamin K2 (1-10 mg/kg daily for 10weeks) inhibited the atherosclerotic plaque progression in the aorta andpulmonary arteries (Kawashima, H., Y. Nakajima, Y. Matubara, J.Nakanowatari, T. Fukuta, S. Mizuno, S. Takahashi, T. Tajima, and T.Nakamura, 1997, Effects of vitamin K2 (menatetrenone) on atherosclerosisand blood coagulation in hypercholesterolemic rabbits, Jpn J Pharmacol75:135-43). Vitamin K2 was also seen to reduce total cholesterol levels,lipid peroxidation, ester cholesterol deposition in the aorta and factorX activity in plasma compared to the control group. A study involvingmore than 500 postmenopausal women investigated the relation betweenvitamin K1 and K2 intake and coronary calcification. Sixty-two percentof the women sampled for the study had coronary calcification. OnlyVitamin K2 intake was associated with the trend toward decreasingcoronary calcification (Beulens, J. W., M. L. Bots, F. Atsma, M. L.Bartelink, M. Prokop, J. M. Geleijnse, J. C. Witteman, D. E. Grobbee,and Y. T. van der Schouw, 2009, High dietary menaquinone intake isassociated with reduced coronary calcification, Atherosclerosis203:489-93).

Both in vivo and in vitro studies have demonstrated that Vitamin K2 hasanticancer effect. A multi-cancer study in Japan was performed to testthe effect of Vitamin K2 on MDS and post-MDS acute myeloid leukemiapatients. Vitamin K2 dosage ranged from 20-135 mg/day orally or 10-50mg/day intravenously. Vitamin K2 was effective in reducing blast cellnumbers in bone marrow and/or peripheral blood in ˜71% of thosereceiving other medication concomitantly (Takami, A., S, Nakao, Y.Ontachi, H. Yamauchi, and T. Matsuda, 1999, Successful therapy ofmyelodysplastic syndrome with menatetrenone, a vitamin K2 analog, Int JHemotol 69:24-6). Another study involving 121 patients withhepatocellular carcinoma undergoing conventional therapy has shown thatwhen patients were given 45 mg/day oral vitamin K2, there was asignificant increase in survival (Jancin, B, 2002, Vitamin K cutshepatocellular CA mortality, Fam Pract News 32). A recent studydemonstrated that there is inverse association between vitamin K2 andprostate cancer. Higher intake of vitamin K2 might reduce prostatecancer risk by 35%. The association was stronger with advanced prostatecancer incidents. Interestingly, Vitamin K2 from dairy products hadstronger effect compared to other sources of vitamin K2 like meat andmeat products (Nimptsch, K., S. Rohrmann, and J. Linseisen. 2008.Dietary intake of vitamin K and risk of prostate cancer in theHeidelberg cohort of the European Prospective Investigation into Cancerand Nutrition (EPIC-Heidelberg), Am J Clin Nutr 87:985-92).

Magnesium Chloride is required in relatively large concentrations innormal metabolism. It is recognized that deficiency of magnesium is rareunless it is accompanied by severe losses in other electrolytes such asin vomiting and diarrhea. It is however frequently recognized asdeficient in the modern diet with symptoms such as muscle tremors andweakness. This mineral is important in many enzymatic reactions and willstabilize excitable membranes. Administered intravenously, magnesium mayproduce an anesthetic action and this is indirect evidence of its actionon the vascular wall endothelial component to stabilize and normalizethe surface of the vascular wail.

Heparin is an anti-thrombotic agent capable of reducing plateletaggregation. It may also play a role in vascular endothelialnormalization because heparin is related to chondroiten sulphate, whichappears naturally as a constituent in the vascular wall and plays a rolein the endothelium, which is not fully understood. It has stronganti-inflammatory actions, which appears to be strongly stimulated informulations described herein because of the presence of carbonic acidcapable of neutralizing the acidic charge of heparin. Heparin is adextrorotary glycosaminoglycan, consisting in a mixture of variouspolysacharidic chains, composed of repeated D-glucosamine units and alsoL-idurcnic acid or D-glucuronic acid. Its molecular weight rangesbetween 6,000 Daltons to 30,000 Daltons, which will depend on either theobtainment source or the methodology, employed for its isolation. Theability in prolonging the blood clotting time is the most known heparinproperty. Further to the anti-clotting activity, it also shows enzymaticantiproteolitic activity antithrombin, platelet antilyse, thrombolitic,antiserotonergic, and antihistaminic.

Formulations can comprise one or more anesthetics. Patient discomfort orphlebitis and the like can be managed using anesthetic at the site ofinjection. If used, the anesthetic can be administered separately or asa component of the composition. One or more anesthetics, if present inthe composition, is selected from the group consisting of lignocaine,bupivacaine, dibucaine, procaine, chloroprocaine, prilocalne,mepivacaine, etidocaine, tetracaine, lidocaine and xylocalne, and salts,derivatives or mixtures thereof.

Formulations can comprise other ingredients for the treatment of theorganism as a whole. For example, an anti-oxidant additive and/orpro-oxidant additive can be present. The latter may be an agent thatacts as a preventive, while the former may be an agent that acts totreat a specific medical condition.

Kits are described comprising a magnetic dipole stabilized solution forinjection. In this embodiment, the solution is provided as a sterilecomposition in a vial. The vial can preferably be an injection vial witha membrane that is suitable for inserting a syringe to pull the solutionfrom the vial or a soft I.V. infusion bag. The solution can be providedas a concentrated solution to which a diluent is added prior toinjection. The diluent can be sterile water. The kit may furthercomprise a pre-filled container which contains the diluent. In apreferred embodiment, a soft infusion bag is pre-filled with diluent.Alternatively, the magnetic dipole stabilized solution vial can containa solution that is at a concentration which is suitable for injectionwithout any dilution. Preferably, the solution for injection isisotonic. That is, the solution can contain salt, carbohydrates, such asglucose, NaHCO₃ or amino acids, such as glycine, and is isotonic withblood plasma.

In some embodiments, the kits comprise a first vial containing amagnetic dipole stabilized solution and a second vial containingcomponents to be admixed with the solution to prepare a composition forinjection. The components are listed above. Preferably, the componentsand the solution are combined just prior to administration. Preferably,in this embodiment, the kit comprises a first container containing asolution comprising one or more selected from the group consisting ofvitamins, salts, acids and vitamers, and mixtures thereof; and a secondcontainer containing a magnetic dipole stabilized solution. As describedherein, it is preferable that the magnetic dipole stabilized solution iselectroactivated water. Additionally, the containers can be vials orbags or a combination of both.

Each kit described herein may further comprise instructions for use. Theinstructions will, of course, depend upon the kit itself and whether adiluent is to be used or other components to be admixed with themagnetic dipole stabilized solution prior to administration.

According to U.S. Pat. No. 7,588,488, there are three types ofelectrolyzed water, which can be prepared by electrolysis of waterhaving ions dissolved therein. While not strictly defining, theinventors can generally describe that Type A water is a disinfectantthat kills a large variety of bacteria, viruses, molds, and sporeswithin seconds of contact. When negatively charged ions migrate to theanode, the fluid around the anode develops a reduced pH in theapproximate range of 1.8 to 4.9 and an ORP in the approximate range of+950 to +1450 millivolts (mV). Type A water can be produced as acontinuous stream of clear solution having a pH of 1.8 to 4.9, an ORP of+950 to +1450 mV, and containing 8 to 200 parts per million (ppm) ofHOCl. When Type A water comes in contact with organic material its pHincreases, its ORP drops, and the HOCl dissipates or gases off, thusreturning to ordinary water having a small amount of free chlorine (Cl).So-called Type B water is an effective emulsifier and cleaner havingantimicrobial properties. It is capable of saponifying surfaces uponcontact. Type B water is an alkaline water stream and can be produced asa continuous stream of clear solution produced around the negativeelectrode, i.e., cathode, during electrolysis. This Type B water isbasic with a pH in the approximate range of 9.1 to 12.2. The ORP of TypeB water is in the approximate range of +100 to −980 mV. Type B wateralso contains sodium hydroxide (NaOH) ions in the approximate range of 8to 200 ppm. Type B water is effective in emulsifying oils and lipids andleaves no residue. Safety and toxicity tests show that Type B water isnontoxic at a pH of 9.5 to 12.2 and an ORP from −350 to −950 mV.So-called Type C water is essentially a form of stabilized Type A waterwith a longer shelf life. Type C solution has an ORP in the approximaterange of 0 to +900 mV, a pH value in the approximate range of 5.5 to8.2, and contains HOCl in the approximate range of 8 to 80 ppm.

As described above, the electro-activated solutions with a stablepositive or negative oxidation-reduction potential may be prepared byany method known in the art. Preferably, sterile, purified water iselectro-activated using an open plate palladium-coated electrode in aceramic-type housing of a module containing ferrous and non-ferrousalloys capable of imparting a fixed magnetic field of at least 7.5 Gaussover a period of time, generally at least 1.75 minutes, at a particularflow rate, generally at least 0.75 liter/minute. The electro-activatedwater thus obtained has an initial positive oxidation-reductionpotential (ORP). Positively charged anolyte water is a carrier for thespecies formed during electroactivation. The use of negatively chargedcatholyte water is also contemplated. The electroactivated solution forinjection will preferably have a negative potential from about −990 mVto about −0.0001 mV. The negative potential is prepared by mixing thepositively charged anolyte water with other components described hereinto prepare the MDSS solution for injection. The MDSS for injection canhave an ORP of −70 mV and is preferably aqueous in nature.

The present subject matter is based on the unexpected discovery that theMDSS compositions described herein are useful in treating, amelioratingand preventing many conditions and diseases and symptoms thereof.Without being bound to any theory, it is believed that the compositionsimprove oxygen delivery to the arteries, veins and cardiac muscle andthe transport of anti-oxidants and minerals to the bloodstream bycausing changes in the concentration gradient of the cellular membraneswhich in turn modulate transport of physiological ions, such as sodiumand potassium. In addition, it is believed that the MDSS compositionsimprove membrane permeability and thus increases the rate of transportof the minerals and anti-oxidants in the solution. Furthermore,injection of the compositions into the bloodstream provides for the fastand prompt reaching of high levels of nutrients, anti-oxidants andminerals in the blood. It is believed that as a result of theseproperties of the MDSS compositions described herein, the compositionsare surprisingly effective against a number of conditions and diseases.

The methods of the invention include systemic application of magneticdipole stabilized solutions (MDSS) containing stabilized oxidativespecies selected from the group consisting of H₂O, O2, H₂O₂, Cl₂O, H₃O,O₃ and ClO₂ as described herein.

The present invention is further described herein by the followingnon-limiting examples which further illustrate the invention, and arenot intended, nor should they be interpreted to, limit the scope of theinvention.

EXAMPLES

1. Method of Preparing Magnetic Dipole Stabilized Solution (MDSS)

The following table describes the preparation of MDSS (also referred toas electroactivated water).

Preferred Values 1. FORMULA Sodium Chloride USP/EP/BP 50 g to 200 g/LSodium Bicarbonate USP/EP/BP 20 to 96 g/L Water for Injection USP 1000mL 2. PREPARATION Collect Water for Injection in a suitable,pre-sterilized and depyrogenated glass container. Add Sodium Chlorideand Sodium Bicarbonate (pre-weighed quantities) to the WFI and mix untilcompletely dissolved. Addition of heat may be required at a temperaturenot exceeding 37° C. Check concentrations of sodium chloride and sodiumbicarbonate Limits: NaCl: 50-200 g/L NaHCO_(3:) 20-96 g/L Releasesolution for use in MDS preparation Prepare fluid path withpre-sterilized components, couplers and tubing. Check machine set-up todeliver suitable flow-rate Limit: 20 mL to 250 mL per minute Discard 2Litres of initial effluent. Measure oxidation reduction potential (ORP)ORP: 450-1500 mV Measure solution pH pH: 3.20-7.60 Determine surfacetension Limit: 45-66 dynes/cm Determine ionic species: HClO, ClO₂, O₃,O₂, HO₂ Limit: NLT 0.01% Collect prepared solvent in pre-sterilizedcontainer 3. QUALITY Measure oxidation reduction potential (ORP) ORP:450-1500 mV CONTROL Measure solution pH pH: 3.20-7.60 Determine surfacetension Limit: 45-66 dynes/cm Determine ionic species: HClO, ClO₂, O₃,O₂, HO₂ Limit: NLT 0.01%2. Specific Formulations

a. In one embodiment, a specific formulation for injection comprises:

Concentration/dose Comment Imidazole HCl 10 mg Lidocaine HCl 200 mgCalcium Gluconate 200 mg Thiamine 15 mg Riboflavine 3 mg Nicotinamide150 mg Pyridoxine 7.5 mg Dexpanthenol 7.5 mg Ascorbate Na 50.0 mgDextrose   5% Caloric source Benzyl Alcohol 0.5% PreservativeTetracycline HCl 350 mg Water 20 ml

b. In one embodiment, a two-container formulation for injectioncomprises:

Concentration/dose Comment VIAL 1 Lidocaine HCl 200 mg Thiamine 15 mgRiboflavine 3 mg Nicotinamide 150 mg Pyridoxine 7.5 mg Dexpanthenol 7.5mg Ascorbic acid 50.0 mg Calcium gluconate 0.2 g Dextrose   5% BenzylAlcohol 0.5% Neutral bicarbonate ECA ORP 400-700; pH 7.0 VIAL 2 HeparinNa 1000 I.U. Sodium Bicarbonate 8.5% Anolyte + ORP Solvent &preservative

c. In one embodiment, a two-container formulation for injectioncomprises:

Container 1 is a vial, which contains a MDSS as described herein as amulti-component injection including a multivitamin combination withminerals, a single amino acid, amino-acetic acid and a local anaesthetic(lidocaine). Container 2 comprises a carrier solution/solvent system,used for dissolution of the components in a physiological buffer which,when combined with Container 1, stabilizes the components for effectivedelivery to the biophase. This solvent system is prepared from sterileWater For Injection (WFD, which contains a small amount of carbonicacid, derived from NaHCO₃. The solvent carries a strong positive ornegative electrical charge, as selected for the application. The chargemay be monitored by accurate oxidation potential measurements to be atleast 800 milli Volts. During dissolution and filling of the injection,the charge may be diminished to about −400 to about −700 milli volts andduring storage and shelf life may diminish further to about −70 milliVolts, which is still considered as adequate and effective. The localanaesthetic action is employed to stabilize the membrane of the vascularendothelial cells by blocking of the sodium channels and providingvascular wall relaxation. Both containers are to be diluted before use.The final dose is 200 ml containing 0.9% Sodium Chloride Injection. Thefinal dose can be provided in an infusion bag.

d. In one embodiment, a specific formulation. REV-1 for injection:

Concentration per dose Comment Sodium ascorbate 395 mg Magnesiumchloride 2 H₂O 255 mg 2-di methyl amino ethanol HCl 200 mg Thiamine 36mg Riboflavine 7.3 mg Nicotinamide 100 mg Pyridoxine 18.2 mg Calciumpantothenate 18.2 mg Cyanocobalamin 320 μg ECA water ORP > 800 10 mlSolvent & preservative

e. In one embodiment, a specific formulation for injection comprises:

Formulation Optional Per dose Total Dose ingredients Ascorbic acid 1000mg 1000 mg Sodium ascorbate/ Ascorbic acid 2-dimethyl amino 300 mg 300mg 2-dimethyl amino ethanol ethanol Aminoacetic acid Ca-d-pantothenate2.40 mg 2.40 mg Ca-d-pantothenate Niacinamide 1100 mg 1100 mgNiacinamide Nicotinic acid Pyridoxine 1100 mg 1100 mg PyridoxineRiboflavin 300 mg 300 mg Riboflavin NAD/co Q10 Thiamine 60.50 mg 60.50mg Thiamine Cyanocobalamin 1500 μg 1500 μg Cyanocobalamin Magnesium 0.6g + 0.4 g 0.90 g Vial I + vial II Magnesium sulphate 4.05 mM Mg⁺⁺sulphate Sodium 0.85 g 0.85 g Buffer vial II Sodium BicarbonateBicarbonate Heparin Na — 1000 IU/ml Heparin Na MDSS Water 10 ml ORP >900 mV Activator MDSS Water pH 5.5-7.6 Alfa lipoic acid Vitamin EDose/10 ml 75 mg Phosphatidile serine 150 mg Glycerophosphatidilecholine Ca + Mg 200 mg Acetyl-L- carnitine Ca-d-pantothenate 2.40 mg1000 mg L tyrosine Niacinamide 1100 mg 20 mg 5 HTP 850 mg Aspartic acidPyridoxine 1100 mg 0.2 mg selenium Riboflavin 300 mg 0.1 mg copper 1 mgzinc 0.1 mg iodine 500 mg glutathione

f. In one embodiment, a specific formulation for injection comprises:

Ingredient Amount Molar Hydrochloride salt of 2-(diethylamino)-N-0.055M-0.076M (2,6-dimethylphenyl) acetamide Fructose 3.5 to 5.5%Nicotinic Acid 0.95 to 1.25% Thiamine 0.85 to 1.45% Riboflavin 0.15 to0.19% Folic Acid 0.25 to 0.55% Pyridoxine 0.15 to 0.19% Ascorbic acid2.30 to 2.50% Cyanocobalamin 0.05 to 0.07% MDSS to 10 ml.

All of the above ingredients in this specific formulation are combinedinto a solution of MDSS that results in a negative electrical potentialof preferably about −120 mV to about −20 mV. Most preferably, thepotential is about −70 mV. The ingredients are introduced into thevehicle by addition of ascorbic acid followed by the vitamin andcarbohydrate constituent. Then, the non-ionized lipid solublecomponents, previously solubilized in a high speed mixer for about 5minutes by means of beta cyclodextrin. The ingredients are combined byslow agitation with addition of an inert gas such as nitrogen to themixture so as to minimize oxidation from taking place. The resultantsolution is then transferred to a glass 10 ml vial under an inertatmosphere such as nitrogen. Each vial is then sealed by means of astopper and an aluminium cap, which is crimped around the seal so as toensure that the seal is hermetic.

g. In one embodiment, a specific formulation for injection comprises:

Amount (Molar Ingredient concentration) Hydrochloride salt of2-(diethylamino)-N- 0.055M-0.076 (2,6-dimethylphenyl) acetamide BetaCyclodextrin hydrate 0.01-0.05 Hydrochloric acid to pH 3.2 NicotinicAcid 0.95 to 1.25% Thiamine 0.85 to 1.45% Riboflavin 0.15 to 0.19% FolicAcid 0.25 to 0.55% Pyridoxine 0.15 to 0.19% Ascorbic acid 2.30 to 2.50%Cyanocobalamin 0.05 to 0.07% Magnetic Dipole Stabilized Solution to 10ml

h. In one embodiment, a specific formulation for injection comprises:

Amount Molar Ingredient concentration Hydrochloride salt of2-(diethylamino)-N- 0.055M-0.076M (2,6-dimethylphenyl) acetamideBetacyclodextrin hydrate 0.01-0.50 mg Sodium Chloride  380-450 mgPhosphate buffer to pH 7.0 Nicotinic Acid 0.95 to 1.25% Thiamine 0.85 to1.45% Riboflavin 0.15 to 0.19% Folic Acid 0.25 to 0.55% Pyridoxine 0.15to 0.19% Ascorbic acid 2.30 to 2.50% Cyanocobalamin 0.05 to 0.07%Magnetic Dipole Stabilized Solution to 10 ml to 10 ml

i. In one embodiment, a specific formulation for injection comprises:

Amount Molar Ingredient concentration Hydrochloride salt of2-(diethylamino)-N- 0.055M-0.076M (2,6-dimethylphenyl) acetamideHydroxypropylcyclodextri n 0.01-0.50 mg Sodium Chloride  380-450 mgPhosphate buffer to pH 7.0 Sodium Hydroxide to pH 7.4 Nicotinic Acid0.95 to 1.25% Thiamine 0.85 to 1.45% Riboflavin 0.15 to 0.19% Folic Acid0.25 to 0.55% Pyridoxine 0.15 to 0.19% Ascorbic acid 2.30 to 2.50%Cyanocobalamin 0.05 to 0.07% Mannitol 2.5% Magnetic Dipole StabilizedSolution to 10 ml to 10 ml3. Clinical Data

a. Effect of the Formulations of the Invention on Different Diseases andConditions

No. Std. Symptom or of Follow Dosage of Improvement Condition Diagnosispatients up Freq. Formulation Care Stage Score General Interviews 50 orSome 1-2 × REV-1 N/A 1 2 or better Indications and more patients per(Cosmetic, consultations are week chronic returning fatigue, stress foretc.) treatment Diabetic ulcer Consultation 10 or Yes 14 Heparin Yes 3New growth of more (1 × included plus toe nail and week) bufferedtotally pain free anolyte Mid shaft Yes 12 Heparin Yes 4 Able to walkfracture non (1 × included plus without a healing week) buffered crutchwithin 6 anolyte weeks Heart disease Yes 12 REV-1 Yes 4 Chest pains (3 ×disappeared week) Coronary MRI + ECG 1 Yes 7 REV-1 Yes 3 Normal heartartery disease function Perivascular Consultation + 2 Yes 27 Heparin Yes2 Patient fully disease scan (1 × included plus mobile, pain affectingweek) buffered free and able to lower limbs anolyte drive Coronary MRI +ECG 1 Yes 14 REV-1 Yes 3 Heart disease artery disease (1 × cured after14 week) weeks Severe Scan and 1 Yes 40 Heparin Yes 4 Fully mobileintermittent Doppler (1 × included plus and able to claudication. week)buffered work after 25 (Femoral anolyte weeks artery) Peri-vascular Scanand 1 Yes 18 Heparin Yes 3 Pain free and disease Doppler (2 × includedplus wound of week) buffered previous anolyte amputation healed Diabeticwith Clinical 1 Yes 24 REV-1 Yes 2 Marked renal (2 × improvementinsufficiency week) after 12 weeks Painful leg Consultation 1 Yes 7intra- Heparin Yes 3 Totally pain after arterial included plus free andable to amputation injections buffered wear prosthesis and fall onanolyte patella Ulcer on toe Consultation 1 Yes 17 Heparin Yes 4 Fullymobile (1 × included plus after 8 weeks week) buffered and pain freeanolyte Buergers Consultation 1 Yes 16 REV-1 Yes 4 Lesions disease (1 ×completely week) healed and pain free Coronary MRI + ECG 1 Yes 32 REV-1Yes 3 (80- VEF from 10% artery disease (1 × year to 51% week) oldimprovement patient) Small Consultation 1 Yes 3 REV-1 Yes 2 Ulcertotally varicose vein (1 × disappeared ulcer week) Intermittent Scan and1 Yes 14 REV-1 Yes 3 Fully mobile, claudication Doppler (1 × no crampingweek) Heart disease MRI + ECG 1 Yes 150 REV-1 Yes 3 No more chest (2 ×pains week) Large ulcer on Consultation 1 Yes 14 REV-1 Yes 4 Ulcerindicates mid shaft (1 × closure. Had week) been present for 14 yearsArterial & Consultation 1 Yes 26 Heparin Yes 2 Fully recovered venousand Doppler (1 × included plus circulation week) buffered disorderanolyte Gangrenous Consultation 1 Yes 40 Heparin Yes 4 Walking fine foot(2 × included plus (severe following week) buffered developed partialanolyte gangrene) amputation Severe burns Consultation 1 Yes 15 REV-1Yes 3 Treated on on both legs (2 × right leg only - week) after 10 weeksimprovement and no infection Calcium Scan, MRI, 20 Yes 12-18 REV-1 Yes1-3 See summary Agatston clinical (1-2 × report Score Patients bloodtests week) (Study) Performance Consultation 1 Yes 12 REV-1 Yes 1Improvement enhancement (1 × (+ Vit. C) in athletic week) performance(Ongoing) and general circulation Hearing loss Auditory 1 Yes 12 REV-1Yes 3 Dramatic in one ear impairment (1 × improvement week) ChronicConsultation 1 Yes 20 REV-1 Yes 4 Dramatic fatigue and (2 × improvementin poly- week) general health pharmacy (Ongoing) including user, lowiron increase in levels ferritin levels Severe Very high 1 Yes 12 REV-1Yes 4 Dramatic and diabetic Type Agatston (1 × sustained II, heart scoreweek) improvement in disease Calcium score and control of sugar levelsSevere High risk 1 Yes 80 REV-1 Yes 3 Dramatic and diabetic Type cardiac(Voluntary) (2 × sustained II, heart disease and week) improvement indisease - Diabetes (Ongoing) Calcium score Genetic Type II and controlof predisposition sugar levels

b. Treatment and Amelioration of Symptoms of Acne.

Three patients were given 1 or 2 infusions a week of REV-1 for a minimumof ten weeks. The results show:

One patient had an improved acne condition after just the 4th treatment.

One patient had less obvious scarring due to acne.

One patient had improved facial color.

Hydration of the skin improved in two patients. As a result, lessmoisturizer was needed.

Two patients had less wrinkles during and after treatment.

c. Metal Ion Removal

The following describes the ability of a MDSS composition to removemetal ions. Twenty male and female individuals between the ages of 24and 63 were randomly selected for the treatment, based on age, physicalactivity and body mass index (BMI). Subjects with a family history ofcardiovascular diseases, diabetes mellitus or cancer were included inthe treatment. The individuals were subjected to a complete physicalexamination, blood and urine analyses, calcium score measurement andradiological examination.

The coronary calcium scan is a test that detects the presence and amountof calcium in a coronary artery and correlates that data to plaqueformation. The calcium score was 0 in nine subjects; 1 in one subject;24 in two subjects; 32 in one subject; 40 in one subject; 42 in onesubject; 46 in one subject; 57 in one subject; 155 in one subject; 482in one subject; and 1668 in one subject. The radiological studyperformed on the twenty individuals showed that individuals with acalcium score of 0 had no calcified plaques, whereas subjects with acalcium score between 24 and 57 had calcified plaques in the leftanterior descending artery (LAD). Subjects with a calcium score of 155or 482 showed calcification in the right coronary artery (RCA) and leftanterior descending artery (LAD). The patient with a calcium score of1668 showed calcification of the right coronary artery, left mainartery, left anterior descending artery (LAD), the diagonal andcircumflex arteries.

All subjects had their blood pressure and pulse taken before and aftereach treatment session and treated with a magnetic dipole stabilizedsolution which is an electro-activated solution prepared as follows.

An electro-activated aqueous solution is prepared using an open platepalladium-coated electrode in a ceramic-type housing of a modulecontaining ferrous and non-ferrous alloys capable of imparting a fixedmagnetic field of at least 7.5 Gauss over a period of time of at least1.75 minutes at a flow rate of at least 0.75 liter/minute. Theelectro-activated water thus obtained, which has an initial positiveoxidation-reduction potential (ORP) in a range between +700 mV and +900mV, is then collected in a sterilized, air-free and endotoxin-freevessel and used to prepare Solution A and Solution B. Both solutions areused as a diluent for vitamins, salts and minerals.

1.0 liter of Solution A is prepared by dissolving the followingvitamins, salts and minerals:

Magnesium Sulphate hexahydrate 60.2 g/L 2-diethylaminoaceto, xylidide30.0 g/L Niacinamide 9.90 g/L Puridoxin HCl 9.90 g/LRiboflavin-5-phosphate sodium 0.19 g/L Thiamin HCl 6.05 g/LCyanocobalamin crystalline 0.18 g/L Electrochemically activated water+007.50 ml

Ascorbic acid, which is a strong anti-oxidant, is added in aconcentration of 88.0 g/L and 95.0 g/L, respectively, to reach a stable,negative ORP in a range between −500 mV and −900 mV.

To prepare Solution B, sodium bicarbonate, sodium chloride, magnesiumsulfate and calcium are added to increase ionization and produce astably charged anti-inflammatory solution. A stabilizer may be alsoadded to the solution in an amount of 0.5% mass/volume to increaseconductive ionization and produce a stably charged solution with astable, positive oxidation-reduction potential in a range between +500mV and +900 mV. The stabilizer may be mixed into the solution byagitation or a sonicator bath and the solution is immediately sealed toprevent entry of oxygen.

1.0 liter of Solution B is prepared by dissolving the following saltsand minerals:

Sodium Bicarbonate USP 86.70 g/L Magnesium Sulphate hexahydrate 20.2 g/LElectrochemically activated water+ 998.5 ml

Both solutions A and B are stable for a period of at least 12 monthswhen stored at 20 degrees-34 degrees Celsius.

Solution A and Solution B are then mixed immediately prior toadministration to produce a stable composition with a stable negativeoxidation-reduction potential (ORP) in a range between −50 mV and −150mV, a stable pH between 6.6 and 7.9, and a conductivity in the rangebetween 11 and 14 mS/cm.

The final mixture thus obtained comprises the following ingredients:

Magnesium sulfate hexahydrate  0.5-10% Sodium Bicarbonate  0.5-10%Ascorbic Acid  5.0-20% Niacinamide 0.2-2.0% Pyridoxin HCl 0.005-0.2% Calcium D Pantothenate 0.01-2.0%  Thiamin HCl 0.1-1.0% Riboflavin0.01-0.1%  Cyanocobalamin 0.001-0.1%  Magnetic Dipole Stabilized Water5.0-500 ml 2-di-ethylaminoethanol 1.0-3.0%

The solution was administered to each subject by intravenous injectionin an amount of 100 ml of sterile diluent (0.9% sodium chlorideinjection) for 35 to 55 minutes once or twice a week for a periodranging from two weeks to two months.

The calcium score was measured in the individuals subjected to thetreatment with the electro-activated solution at the end of treatment.Table 3 below shows the calcium score of nine individuals with aninitial medium to high calcium score before and after 12 treatmentsessions. The data in Table 1 clearly show a positive effect of thetreatment on individuals with an initial calcium score of 46 and above.

Calcium Score Percentage Calcium Score After 12 Treatment of IncreasePatient Before Treatment Sessions or Decrease 1 24 25 4% Increase 2 2426 8% Increase 3 32 31 3% Decrease 4 40 42 5% Increase 5 46 29 37%Decrease 6 57 40 29% Decrease 7 155 121 22% Decrease 8 482 441 9%Decrease 5 1668 1539 8% Decrease

The magnetic dipole stabilized solutions described herein aresurprisingly effective at removing metal ions. Especially preferredmagnetic dipole stabilized solutions for this purpose further compriselipoic acid in the amounts described elsewhere herein.

d. General Malnutrition

The following describes the ability of a MDSS composition to treatmalnutrition symptoms. A dose of one infusion per week containing theREV-1+formulation described above was administered. The trial lasted tenweeks. Subject Data: The subjects had malnutrition problems. Somesubjects presented with type II diabetic symptoms. Results: One patientstated feeling very good after treatment. Prior to treatment, skin colorof ankles was blue. After treatment, the color is pink. Another patientpresented with improved hydration in the eyes (electroactivated waterwas used as eye drops as well), and increased blood circulation. Anotherpatient reported feeling very good with improvement in blood supply toareas of a hand injury. Another patient reports overall well-being andimprovements at the same weight, indicating a positive nutritionaleffect. Other patients report feeling more energetic. One patientreported feeling more energetic and pain in the heel area had improved.

e. Improved Athletic Performance

The formulation, REV-1 was administered to a subject. The subjectreceived 1 treatment per week up to two weeks prior to the event atwhich time the subject received two treatments per week until the event.After only four treatments, subject noticed an improved running time for91 km as compared to time before treatment. In a follow-up trial, thesubject was given six treatments one year later and again the subjectreported higher energy levels during the race.

Throughout this specification and the claims, the words “comprise,”“comprises,” and “comprising” are used in a non-exclusive sense, exceptwhere the context requires otherwise.

As used herein, the term “about,” when referring to a value is meant toencompass variations of, in some embodiments ±20%, in some embodiments±10%, in some embodiments ±5%, in some embodiments ±1%, in someembodiments ±0.5%, and in some embodiments ±0.1% from the specifiedamount, as such variations are appropriate to perform the disclosedmethods or employ the disclosed compositions.

All publications, patent applications, patents, and other references areherein incorporated by reference to the same extent as if eachindividual publication, patent application, patent, and other referencewas specifically and individually indicated to be incorporated byreference. It will be understood that, although a number of patentapplications, patents, and other references are referred to herein, suchreference does not constitute an admission that any of these documentsforms part of the common general knowledge in the art.

Although the foregoing subject matter has been described in some detailby way of illustration and example for purposes of clarity ofunderstanding, it will be understood by those skilled in the art thatcertain changes and modifications can be practiced within the scope ofthe appended claims.

Having thus described in detail preferred embodiments of the presentinvention, it is to be understood that the invention defined by theabove paragraphs is not to be limited to particular details set forth inthe above description as many apparent variations thereof are possiblewithout departing from the spirit or scope of the present invention.

What is claimed is:
 1. A composition comprising the product of mixingcontents of a first vial with contents of a second vial in a 1:1 ratio,the first vial containing an aqueous solution comprising water forinjection (WFI), ascorbic acid, thiamine HCl, magnesium sulfate,cyanocobalamin, a B-vitamin, pyridoxine HCl, riboflavin-5′-phosphate,calcium D-pantothenate, and sodium chloride; the second vial containingan aqueous solution comprising water for injection (WFI) sodiumbicarbonate, and sodium chloride, wherein at least one of the aqueoussolution in at least one of the first vial or the second vial furthercomprises an antibiotic, the aqueous solution in the first vial has anelectrical potential of +1000 to +1300 prior to mixing, and the aqueoussolution in the second vial has an electrical potential of +5 to +700prior to mixing, wherein the composition has an electrical potential of−1 to +200 and 4.047% to 4.947% by weight of the ascorbic acid, 0.285%to 0.349% by weight pf the thiamine HCl, 3.636% to 4.444% by weight ofthe magnesium sulfate, 0.0085% to 0.011% by weight of the cyanobalamin,0.5345% to 0.6535% by weight of the B-vitamin, 0.5345% to 0.6535% byweight of the pyridoxine HCl, 0.012% to 0.014% by weight of theriboflavin 5′-phosphate, 0.013% to 0.016% by weight of the calciumD-pantothenate, 2.10% to 6.30% by weight of the sodium bicarbonate,0.0009% to 0.0011% by weight of the sodium chloride, and the antibioticafter mixing.
 2. The composition of claim 1, wherein the B-vitamin is aform of vitamin B3.
 3. The composition of claim 2, wherein the form ofvitamin B3 is niacinamide.
 4. The composition of claim 1, whereinconcentrations in the first vial are 8.9933% by weight ascorbic acid,0.6333% by weight thiamine HCl, 8.080% by weight magnesium sulfate,0.0193% by weight cyanocobalamin, 1.188% by weight of niacinamide,1.188% by weight pyridoxine HCl, 0.0253% by weightriboflavin-5′-phosphate, 0.0293% by weight calcium D-pantothenate, and0.001% sodium chloride, and concentrations in the second are 8.40% byweight sodium bicarbonate, and 0.001% by weight sodium chloride.
 5. Amethod of treating or ameliorating a skin condition, a conditionassociated with diabetes, a condition associated with a cardiovasculardysfunction, a cancer, an infection, symptoms of menopause, or metalpoisoning in a subject in need thereof, or reducing the amount of metalin a subject in need thereof, or increasing metal excretion from asubject in need thereof, or enhancing performance of a subject orproviding nutrition support to a subject in need thereof, comprisingadministering to a subject in need thereof the composition of claim 1 byinjection administration.